ARTICLE | doi:10.20944/preprints202104.0225.v1
Online: 8 April 2021 (10:11:23 CEST)
In cancer, the lymphatic system is hijacked by tumor cells to escape from primary tumor and to metastasize to the sentinel lymph nodes. Tumor lymphangiogenesis is stimulated by the vascular endothelial growth factors-C (VEGFC) after binding to its receptor VEGFR-3. However, how VEGFC cooperates with other molecules to promote lymphatic neovessels growth is not fully determined. Here, we found that tumor lymphangiogenesis developed in tumoral lesions and in their surrounding adipose tissue (AT). Interestingly, lymphatic vessel density correlated with an increase of circulating free fatty acids (FFA) in the lymph from tumor-bearing mice. We found that adipocyte-released FFA are uploaded by lymphatic endothelial cells (LEC) to stimulate their sprouting. Lipidomic analysis identified the monounsaturated oleic acid (OA) as the major circulating FFA in the lymph in tumoral context. OA transporters FATP-3, -6 and CD36 were only upregulated on LEC in the presence of VEGFC showing a collaborative effect of these molecules. OA released from adipocytes is taken up by LECs to stimulate the fatty acid β-oxidation, leading to increase adipose tissue lymphangiogenesis. Our results provide new insights on the dialogue between tumors and adipocytes via the lymphatic system and identify a key role for adipocyte-derived FFA in the promotion of lymphangiogenesis, revealing novel therapeutic opportunities for inhibitors of lymphangiogenesis in cancer.
REVIEW | doi:10.20944/preprints202210.0206.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: fatty acid desaturases; highly unsaturated fatty acids; unusual unsaturated fatty acids; sciadonic acid; sapienic acid; mead acid
Online: 14 October 2022 (09:37:18 CEST)
The human chromosome 11q13 (HSA 11q13) genomic locus is a major cancer hotspot and has been established as the most frequently altered by amplification in a variety of human cancers. The fatty acid desaturase genes (FADS1, FADS2 and FADS3) localize to the 11q12- 13.1 region. FADS2 activity is promiscuous, catalyzing biosynthesis of polyunsaturated and monounsaturated fatty acids, including unsaturated branched chain fatty acids (BCFA) by Δ6, Δ8, and Δ4 desaturation toward at least 16 substrates. Our main aim here is to review known and putative consequences of FADS2 dysregulation due to effects on the 11q13 locus in various cancer types. We searched PubMed and Google Scholar databases for articles that showed 11q13 amplification and studies reporting FADS2 function in various cancer types. FADS2 silencing causes synthesis of sciadonic acid (ScA, 5Z,11Z,14Z-20:3) in MCF7 cells and breast cancer in vivo. 5Z,11Z,14Z-20:3 is structurally identical to the eicosanoid precursor arachidonic acid (5Z,8Z,11Z,14Z–20:4) except it lacks the internal Δ8 double bond required for prostaglandin and leukotriene synthesis, among other eicosanoids. Melanoma, prostate, liver and lung cancer cells insensitive to SCD inhibition show increased FADS2 activity leading to sapienic acid (16:1n10) biosynthesis from 16:0. Elevated serum mead acid (20:3n-9) levels were found in more than a third of hepatocellular carcinoma patients, indicative of an unsatisfied demand for arachidonic acid, likely as a substrate for eicosanoids. A highly expressed circular RNA (hsa_circ_022382) within an exonic region of FADS2 is associated with shorter overall survival in colorectal cancer patients. Similarly, in lung cancer tissues circFADS2 RNA is highly expressed. Palmitic acid (16:0) is a common substrate for SCD and FADS2. FADS2 circular RNAs are at high levels in colorectal and lung cancer tissues. The evidence thusfar supports an effort for future research on the role of FADS2 as a tumor suppressor in a range of neoplastic disorders.
ARTICLE | doi:10.20944/preprints201911.0132.v1
Subject: Biology, Animal Sciences & Zoology Keywords: marula; seed (kernel) cake; fatty acids; fatty acid totals; fatty acid ratios; atherogenicity and desaturase indices
Online: 12 November 2019 (16:25:03 CET)
Marula seed cake (MSC) is a nutritionally-rich natural feed resource that can enhance the healthiness of animal-derived foods (ADFs) for human consumption. This study compared the health-related fatty acid (FA) profiles of MSC products from South Africa and Eswatini. Composite samples monthly collected from both countries were analysed for FAs. MSC products from both countries were found to be dominated by oleic acid (>70%), followed by palmitic, linoleic and stearic acids. Consequently, both products had their FA totals dominated by ƩMUFA followed by ƩSFA, ƩPUFA, Ʃn-6 PUFA and Ʃn-3 PUFA. Both oleic and stearic acids were higher (P < 0.01) whilst linoleic (P < 0.001), α-linolenic (P < 0.05), margaric (P < 0.05), palmitoleic (P < 0.05) and eicosatrienoic (P < 0.05) acids were lower in South African in comparison to Eswatini MSC. Consequently, South African MSC had higher ƩMUFA (P < 0.01) but lower ƩPUFA (P < 0.001), Ʃn-6 PUFA (P < 0.001) and Ʃn-3 PUFA (P < 0.05). Also, Eswatini MSC had higher n-6 : n-3 PUFA, PUFA : SFA (P = 0.001) and PUFA : MUFA (P < 0.05) ratios. Further, MSC products from both countries had similarly (P > 0.05) low atherogenicity and high desaturase indices. In conclusion, both country products are rich particularly in oleic acid and their incorporation into farm animal diets would increase content of the MUFA in ADFs and, consequently, improve health benefits to human consumers.
ARTICLE | doi:10.20944/preprints201905.0184.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: Acrosome reaction; Polyunsaturated fatty acid; Sperm; Pigs
Online: 15 May 2019 (10:35:25 CEST)
This study investigated the relationship of acrosome reactions and fatty acid composition on fertility in boar sperm. The acrosome reaction of sperm was induced via methyl-beta-cyclodextrin (MBCD), and acrosome reaction, plasma membrane integrity, and fertility were analyzed. The fatty acid composition of the excess acrosome reacted sperm was determined via gas chromatography. The results showed that the acrosome reaction in sperm was induced over 85% of the time by 60 mM MBCD treatment, and the plasma membrane integrity was significantly decreased and was dependent on the MBCD level. The acrosome reacted sperm resulted in significantly higher saturated fatty acids (SFAs) and lower unsaturated fatty acids (PUFAs) than the non-acrosome reaction group. Moreover, the acrosome reacted sperm from 60 mM MBCD significantly decreased in vitro fertility and blastocyst formation relative to non-acrosome reacted sperm, and the acrosome reaction was positively correlated with SFAs and negatively correlated with PUFAs. Of these fatty acids, C22:5n-6 (docosapentaenoic acid [DPA]) and C22:6n-3 (docosahexaenoic acid [DHA]) were directly negatively correlated with the acrosome reaction (r = -0.982 and -0.947, respectively). In conclusion, the excessive acrosome reactions may occur by reducing the PUFAs, which may then dramatically decrease sperm fertility in pigs.
REVIEW | doi:10.20944/preprints202012.0220.v1
Subject: Biology, Anatomy & Morphology Keywords: chromatography; amino acids; fatty acids; pork analysis; adipose tissue; muscle tissue; nutritional factors.
Online: 9 December 2020 (11:14:18 CET)
The increasing demand for high-quality livestock products dictates to develop approaches to assessing the composition of the fatty acids (CFAs) and amino acids (CAAs) in animal tissues. The review considers the following issues: chromatographic methods for the determination of CAAs and CFAs of pig tissues; factors influencing the CAAs and CFAs of pig tissues; methods of regulating CAAs and CFAs of pork using nutritional factors; the effect of CAAs and CFAs on formation of meat properties. The main methods for determining CAAs or CFAs are the ion-exchange or gas chromatography, respectively. The total FA amount and individual FAs have significant effects on the tenderness, taste, color and juiciness of pork meat (due to the different melting points of particular fatty acids, formation of lipid oxidation products during cooking, etc.). Muscle proteins of pigs with regulated fatness differ also in CAAs (decreasing by increase in “pork fat” and decrease in the protein’s amount. The significance of this review is also determined by high popularity of pork in Russia and in a number of other countries of the world.
ARTICLE | doi:10.20944/preprints201806.0142.v1
Online: 8 June 2018 (16:20:20 CEST)
The aim of this study (first analytical approach) was to obtain data on the fatty acid composition of gluten-free foods (bakery products) for celiac people. The study included 35 different products (snacks, biscuits, bakery products, pasta, flours, etc.) from several manufacturers. After extraction and esterification, the fatty acid content was determined by GC-MS. The monounsaturated fatty acids (MUFAs) are the major constitutes (57%) of the fatty acids pool followed by saturated fatty acids (SFAs) (30%) and polyunsaturated fatty acid (13%). Only fifteen, of the thirty-five gluten free samples analyzed, provide adequate energy intake, while in eleven samples, saturated fatty acids take more energy than that recommended by EFSA. It has emerged that local producers generally use the finest raw materials (olive oil, etc.) compared to the industries which, as has been pointed out, in many cases use palm and palm kernel oils although gluten free commercial products are high added value foods, expensive and intended for a particularly sensitive public.
ARTICLE | doi:10.20944/preprints202208.0073.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: extravillous trophoblast; placenta; saturated fatty acid; in-utero environment; MRP1
Online: 3 August 2022 (04:21:58 CEST)
Normal function of placental extravillous trophoblasts (EVTs), which are responsible for uteroplacental vascular remodeling, is critical for adequate delivery of oxygen and nutrients to the developing fetus and normal fetal programming. Proliferation and invasion of spiral arteries by EVTs depends upon adequate levels of folate. Multidrug resistance-associated protein 1 (MRP1), which is an efflux transporter, is known to remove folate from these cells. We hypothesized that palmitic acid increases MRP1-mediated folate removal from EVTs, thereby interfering with EVTs’ role in early placental vascular remodeling. HTR-8/SVneo and Swan-71 cells, first trimester human EVTs, were grown in the absence or presence of 0.5 mM and 0.7 mM palmitic acid, respectively, for 72 h. Palmitic acid increased ABCC1 gene expression and MRP1 protein expression in both cell lines. The rate of folate efflux from the cells into the media increased with a decrease in migration and invasion functions in the cultured cells. Treatment with N-acetyl cysteine (NAC) prevented the palmitic acid mediated upregulation of MRP1 and restored invasion and migration in the EVTs. Finally, in an ABCC1 knockout subline of Swan-71 cells, there was a significant increase in invasion and migration functions. The novel finding in this study that palmitic acid increases MRP1-mediated folate efflux provides a missing link that helps to explain how maternal consumption of saturated fatty acids compromises the in-utero environment.
REVIEW | doi:10.20944/preprints202001.0330.v1
Subject: Life Sciences, Molecular Biology Keywords: fatty acyl desaturase; Δ6 - desaturase; long-chain polyunsaturated fatty acid; LC-PUFA; ω3; ω6; EPA; DHA; AA; essential fatty acid; health; fish; transgene
Online: 28 January 2020 (04:39:09 CET)
Fatty acid desaturase 2 (Fads2) is the key enzyme of long chain polyunsaturated fatty acid (LC-PUFA) biosynthesis. Endogenous production of these biomolecules in vertebrates, if present, is insufficient to meet demand. Hence, LC-PUFA are considered as conditionally-essential. At present however, LC-PUFA are globally-limited nutrients due to anthropogenic factors. Attention of research is given therefore to find ways to maximize endogenous LC-PUFA production especially in production species, whereby deeper knowledge on molecular mechanisms of enzymatic steps involved is being generated. This review first briefly informs about the milestones in the history of LC-PUFA essentiality exploration before it focuses on the main aim – to highlight the fascinating Fads2 potential to play roles fundamental to adaptation to novel environmental conditions. Investigations are summarized, which elucidate the evolutionary history of fish Fads2 providing an explanation for the remarkable plasticity of this enzyme in fish. Further, structural implications of Fads2 substrate specificity are discussed and some relevant studies performed on organisms other than fish are mentioned in cases when such studies have so far not been conducted on fish models. The importance of Fads2 in the context of growing aquaculture demand and dwindling LC-PUFA supply is depicted and a few remedies in the form of genetic engineering to improve endogenous production of these biomolecules are outlined.
ARTICLE | doi:10.20944/preprints201807.0240.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Non-alcoholic fatty liver disease; NAFLD; omega-3 fatty acid; EPA; DHA; PUFA;
Online: 13 July 2018 (14:47:22 CEST)
Background & Aims: This RCT aimed to investigate the safety and efficacy of MF4637, a medical food comprising highly concentrated, highly purified, long chain (LC) omega-3 fatty acids, (460 mg eicosapentaenoic acid (EPA) and 380 mg docosahexaenoic acid (DHA)) in correcting the omega-3 fatty acid nutritional deficiency present in non-alcoholic fatty liver disease (NAFLD). The potential for MF4637 to reduce liver fat was evaluated in a subset of patients. Methods: 176 subjects with NAFLD were randomised to receive 3 g/d of LC-omega-3 fatty acids (n=87) or placebo (olive oil; n=89) for 24 weeks, in addition to following standard-of-care dietary guidelines for these patients. Thus, interventions were given on top of the dietary advice. The omega-3 index, omega-6:omega-3 fatty acid ratio (primary outcome) and quantitative measurements of red blood cell (RBC) EPA and DHA (secondary outcome) were determined at baseline and study completion. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) assessment of change in liver fat fraction was conducted in a subset of patients. Results: Of the 176 randomised subjects, 167 were analysed for the primary and secondary outcomes (n=81 in the MF4637 group; n=86 in the placebo group). Supplementation with MF4637 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the omega-6:omega-3 fatty acid ratio in NAFLD patients compared to placebo (p<0.0001). There was a statistically significant reduction in liver fat content within both groups with no difference between them. An inverse relationship between change in absolute RBC EPA+DHA and change in liver fat, AST and ALT levels was seen suggesting that a greater increase in omega-3 content was associated with a reduction for both liver fat content and improvement in liver enzyme levels. Additionally, a significant liver fat-lowering effect of MF4637 compared to placebo was demonstrated in a subset of patients with baseline fatty liver index (FLI) score ≥ 40. There were no serious adverse events related to study interventions. Conclusions: The study results demonstrate that the medical food MF4637, was able to correct the nutritional deficiency of omega-3 in NAFLD patients above and beyond that obtained with nutritional counselling. This demonstrates that MF4637 is beneficial in raising the low omega-3 index observed in these patients. A reduction in hepatic steatosis was demonstrated with both intervention groups although no distinction between groups was seen. Further analyses demonstrate the potential to identify omega-3 sensitive patients using an easily available clinical tool for steatosis prediction.
COMMUNICATION | doi:10.20944/preprints201610.0015.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Blackberry juice; Thermoultrasound; Antioxidant Compounds; Fatty Acids
Online: 7 October 2016 (10:12:21 CEST)
Blackberry (Rubus fruticosus spp) is a fruit that has a significant antioxidant activity, due to its content in anthocyanins and antioxidant compounds. Emerging technologies are required as the thermoultrasound technique that ensures microbial reduction and release of compounds with antioxidant properties. The objective of this study was to evaluate changes in the antioxidant content and fatty acid profile of blackberry juice when it is subjected to conservation treatment (pasteurization and thermoultrasound). The blackberry juice and the extracted oil of blackberry juice with n-hexane (control, pasteurized and thermoultrasonicated) were evaluated in antioxidant activity, fatty acid profile and antioxidant content. The thermoultrasound juice had the highest (p < 0.05) amount of total phenols (1011 mg GAE/L), anthocyanins (118 mg Cy-3-GlE/L); antioxidant activity by ABTS (44 mg VCEAC/L) and DPPH (2665 µmol TE/L) compared to the control and pasteurized samples, as well as, as well as, oil extract of obtained of the thermoultrasound juice presented high antioxidant activity (177.54 mg VCEAC/L to ABTS and 1802.60 µmol TE/L to DPPH). The fatty acid composition of the oil extract showed the presence of myristic, linolenic, stearic, oleic, and linoleic acid, the fatty acid profile was similar in the different samples with the exception of stearic acid where this was higher in control sample. The thermoultrasound treatment can be an alternative to pasteurization treatments because keeps and releases antioxidant bioavailable compounds, preserving their fatty acids.
REVIEW | doi:10.20944/preprints202112.0502.v1
Subject: Biology, Physiology Keywords: Adipose tissue; G-protein coupled receptors; Free Fatty acid receptors; Thermogenesis; Adipogenesis
Online: 31 December 2021 (10:43:17 CET)
Fatty acids (FFAs) are important biological molecules that serve as a major energy source and are key components of biological membranes. Besides, FFAs play important roles in metabolic regulation and contribute to the development and progression of metabolic disorders like diabetes. Recent studies have shown that FFAs can act as important ligands of G-protein coupled receptors (GPCRs) on the surface of cells and impact key physiological processes. Free fatty acid activated receptors include FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41) and FFAR4 (GPR120). FFAR2 and FFAR3are activated by short chain fatty acids like acetate, propionate and butyrate whereas FFAR1 and FFAR4 are activated by medium and long chain fatty acids like palmitate, oleate, linoleate and others. FFARs have generated considerable attention over the last few years and have become attractive pharmacological targets in the treatment of type 2 diabetes and metabolic syndrome. Several lines of evidence point to their importance in the regulation of whole-body metabolic homeostasis including adipose metabolism. Here we summarize our current understanding of the physiological functions of FFAR isoforms in adipose biology and explore the prospect of FFAR based therapies to treat patients with obesity and Type 2 Diabetes.
ARTICLE | doi:10.20944/preprints202204.0079.v1
Subject: Life Sciences, Biochemistry Keywords: fatty acid oxidation; glycolysis; ERK5; metabolic flexibility; metabolic plasticity
Online: 8 April 2022 (11:04:49 CEST)
Cells have metabolic flexibility that allows them to adapt to changes in substrate availability. Two highly relevant metabolites are glucose and fatty acids (FA), and hence, glycolysis and fatty acid oxidation (FAO) are key metabolic pathways leading to energy production. Both pathways affect each other, and in the absence of one substrate, metabolic flexibility allows cells to maintain sufficient energy production. Here we show that glucose starvation or sustained pyruvate dehy-drogenase (PDH) activation by dichloroacetate (DCA) induce a large genetic remodeling to pro-pel FAO. The extracellular signal-regulated kinase 5 (ERK5) is a key effector of this multistep metabolic remodeling. First, there is an increase in the lipid transport by expression of low-density lipoprotein receptor-related proteins (LRP), e.g. CD36, LRP1 and others. Second, an increase of the expression of members of the acyl-CoA synthetase long-chain (ACSL) family acti-vates FA. Finally, the expression of the enzymes that catalyze the initial step in each cycle of FAO, i.e. the acyl-CoA dehydrogenases (ACADs), is induced. All of these pathways lead to enhanced cellular FAO. In summary, we show here that different families of enzymes, which are essential to perform FAO, are regulated by the signaling pathway, i.e. MEK5/ERK5, which transduces changes from the environment to genetic adaptations.
ARTICLE | doi:10.20944/preprints201906.0205.v1
Subject: Biology, Ecology Keywords: freshwater zooplankton; Moina; salinity tolerance; NaCl; fatty acid
Online: 21 June 2019 (08:12:15 CEST)
Salinity is a known factor which shapes population dynamics and community structure through direct and indirect effects towards aquatic ecosystems. The responses of Moina macrocopa (Cladocera) collected from Setiu Wetland lagoon (Terengganu) were evaluated through manipulative laboratory experiments to understand the ability of M. macrocopa to tolerate under high salinity stress. Specifically, the fatty acid composition, growth, survival and reproduction of this cladocerans species were examined. Sodium chloride (NaCl) were used in the treatments water with the concentration 0, 4, 6, 8, 12, and 15psu. Fatty acid levels were determined using Gas Chromatography and Mass Spectrophotometry (GC-MS). Results clearly indicate that normal conditions give the highest content of fatty acid, especially the polyunsaturated fatty acid content like EPA (eicosapentaenoic acid), ALA (alpha-linoleic acid), ARA (arachidonic acid) and DHA (docosahexaenoic acid). Furthermore, M. macrocopa survival also was best at 0psu, with percentage reached 98%, whereas the opposite occurred at 15psu, with approximately 9% of viable animals survived. On other aspects, M. macrocopa also showed the highest reproduction rate at 0psu (e.g. average initial age of reproduction, 4.33±0.58 days) compared with other salinities level. Interestingly, the difference in terms of growth at different salinities was unapparent, an unexpected outcome when adverse effects such as osmoregulation pressure on the organism are considered. Based on the results, we conclude that M. macrocopa can only tolerate salinity below 8psu and, is unable to withstand stressful environmental condition engendered with salinities above 8psu.
ARTICLE | doi:10.20944/preprints202105.0577.v1
Subject: Life Sciences, Other Keywords: Melanoma patients; Small Extracellular Vesicles; Proteomics; Fatty acids; Biomarkers
Online: 24 May 2021 (15:07:09 CEST)
The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is key to increase survival and therapeutic adjustment. Especially in stages II-IV biomarkers are urgently needed for adjuvant therapy purposes after resection and for treatment of metastatic patients. We here investigated if fatty acid (FA) and protein composition of small extracellular vesicles (sEV) deriving from plasma of 0-I, II, and III-IV stage melanoma patients (n=38) could reflect disease stage and thus function as biomarker. The subpopulation of sEV expressing CD81 (CD81sEV) was isolated by an ad hoc immune affinity technique from microvesicle-depleted plasma. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA and a decrease in Saturation Index (C18:0/C18:1), already detectable in early stages, distinguished patients’ from healthy donor CD81sEV. Proteomics (identifier PXD024434) detected an exclusive and significant increase of CD14, PON1, PON3 and APOA5 in stage II and a significant decrease of Rap1b in stage III-IV CD81sEV. The FA and proteomic stage dependent CD81sEV signature strengthens the potential of circulating sEV studies in providing discriminatory information for early diagnosis, prediction of metastatic behavior and follow up of melanoma patients.
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: essential fatty acid semi carbazide; ID50; IL-4; IL-12
Online: 18 February 2020 (11:15:32 CET)
Bacterial infections are world-wide problem and resistant bacteria is increasing globally that lead to treatments failure. Thus, it is important to find new techniques that are effective for the treatment antibiotic-resistant microorganisms. Green medicine used for the medication of different bacterial infection. Therefore , the study aimed to evaluate the immunomodulatory activity of essential fatty acid semi carbazide (EFASC) compounds extracted from flaxseed to eradicate resistance pathogens . Crud extracts of Linum usitatissimum was extracted by hexane for extraction of EFASC. The results of LD50 appear that a live suspension of E.coli was 0.49×107 ,while HK E.coli was 108 , 125 mg /ml were the optimum dose in stimulate immune response of EFASC which gave maximum dose of total WBC , Neutrophil and Monocyte count. The immunomodulatory activity appear that E.coli + EFASC released moderate levels of IL-4 . HK E.coli release higher IL-4 lead to increase the hypersensitivity and hyper responses of immune system. HK + EFASC immunogen revealed moderate increased in IL-12 mean level 0.99 pg /ml, HK bacteria recorded 1.49 pg/ml, while the mean of EFASC revealed no significant different compare with control. An effective protection was observed in immunized groups with HK E.coli and EFASC challenged with 100 of LD50 of a live E.coli.
ARTICLE | doi:10.20944/preprints201809.0595.v1
Subject: Materials Science, Nanotechnology Keywords: nanoemulsion; oral delivery; ω-3 polyunsaturated fatty acid derivative; MDA-MB-231; triple-negative breast cancer
Online: 30 September 2018 (05:14:34 CEST)
Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, ω−3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4’-chloro-3’-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω−3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI<0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.
ARTICLE | doi:10.20944/preprints201804.0078.v1
Subject: Life Sciences, Microbiology Keywords: membrane fatty acids composition; Staphylococcus aureus; staphyloxanthin; membrane fluidity; metabolic regulation
Online: 6 April 2018 (11:37:53 CEST)
Fatty acids play a major role in determining membrane biophysical properties. Staphylococcus aureus produces branched-chain fatty acids (BCFAs) and straight-chain fatty acids (SCFAs), and can incorporate exogenous SCFAs and straight-chain unsaturated fatty acids (SCUFAs). Many S. aureus strains produce the triterpenoid pigment staphyloxanthin, and the balance of BCFAs, SCFAs and staphyloxanthin determines membrane fluidity. Here, we investigated the relationship of fatty acid and carotenoid production in S. aureus using a pigmented strain (Pig1), its carotenoid-deficient mutant (Pig1ΔcrtM) and the naturally non-pigmented Staphylococcus argenteus that lacks carotenoid biosynthesis genes and is closely related to S. aureus. Fatty acid compositions in all strains were similar under a given condition indicating that staphyloxanthin does not influence fatty acid composition. Strain Pig1 had decreased membrane fluidity as measured by fluorescence anisotropy than the other strains under all conditions indicating that staphyloxanthin helps maintain membrane rigidity. We could find no evidence for correlation of expression of crtM and fatty acid biosynthesis genes. Supplementation of medium with glucose increased SCFA production and decreased BCFA and staphyloxanthin production, whereas acetate-supplementation also decreased BCFAs but increased staphyloxanthin production. We believe that staphyloxanthin levels are influenced more through metabolic regulation than responding to fatty acids incorporated into the membrane.
CONCEPT PAPER | doi:10.20944/preprints201804.0115.v1
Subject: Life Sciences, Immunology Keywords: omega-3 and omega-6 polyunsaturated fatty acids; colorectal cancer; cancer immune therapy
Online: 10 April 2018 (08:05:27 CEST)
Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been found to be modulators of immune function. Additionally, they may affect the growth of colorectal cancer (CRC). With the advent of novel treatment approaches in oncology targeting immune checkpoint inhibition and aiming to boost the immune response against tumors the exact role of n-3 and n-6 PUFA in inflammation as well as in CRC needs to be re-evaluated in order to understand potential interactions with these new treatment paradigms. Interestingly, for the cyclooxygenase (COX) inhibitor aspirin a possible synergistic effect together with a PD1-Ligand antibody has been shown. However, could n-3 PUFA be disadvantageous in the context of immune tumor therapy due to an immune suppressive effect that has been described for these fatty acids in the past, or could they also enhance the effect of immune checkpoint inhibition? In this paper, we discuss the current data regarding the immune modulatory as well as the anti-CRC effect of n-3 PUFA. Arguing towards an immune-activating effect of n-3 PUFA, we demonstrate the results of a pilot study. Here, we show that incubation of human peripheral blood mononuclear cells (PBMCs) with the n-3 PUFA docosahexaenoic acid (DHA) significantly decreases CRC-cell supernatant-triggered secretion of IL-10 and increases secretion of TNF-a, while the omega-6 polyunsaturated fatty acid (n-6 PUFA) arachidonic acid (AA) reduced TNF-a secretion. These changes in cytokine secretion upon incubation with DHA demonstrate a possible enhancing effect of n-3 PUFA on an anti-tumor immune response.
ARTICLE | doi:10.20944/preprints202112.0445.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: omega-3; polyunsaturated fatty acids; painful diabetic neuropathy; metabolism; metabolomics
Online: 28 December 2021 (10:58:38 CET)
Background: Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly reported to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. Specifically, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms. However, the molecular mechanism behind omega-3 PUFAs ameliorating pDN symptoms is lacking. Therefore, we sought to determine the distinct cellular pathways that omega-3 PUFAs dietary supplementation promotes in reducing painful neuropathy in type 2 diabetes mellitus (DM2) patients. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the "En Balance-PLUS" diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1,000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data was analyzed using random forest, hierarchical cluster, ingenuity pathway analysis, and metabolic pathway mapping. Results: We found that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (-11%), glycine (+11%) and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253 %) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10-4, z-score = -1.96), peroxidation of lipids (p = 2.24 × 10-5, z-score = -1.944), Ca2+ transport (p = 1.55 × 10-4, z-score = -1.969), excitation of neurons (p = 1.07 ×10-4, z-score = -1.091), and concentration of glutathione (p = 3.06 × 10-4, z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following omega-3 PUFAS supplementation is consistent with using omega-3 PUFAs as a complementary dietary strategy as part of the overall treatment of painful diabetic neuropathy.
ARTICLE | doi:10.20944/preprints201811.0221.v1
Subject: Chemistry, Medicinal Chemistry Keywords: Fatty Acid Amide Hydrolase; cannabinoid; carboxamide inhibitors; 3D-QSAR; CoMSIA.
Online: 8 November 2018 (14:52:23 CET)
Fatty Acid Amide Hydrolase (FAAH) is one of the enzymes responsible of endocannabinoids metabolism. The inhibition of FAAH is a useful and indirect strategy to raise endogenous cannabinoid concentrations, which would be useful for the treatment of various pathological processes in which cannabinoid concentrations are lowered. In the present work, we present an extensive 3D-QSAR/CoMSIA study on a series of 90 irreversible inhibitors of FAAH of pyrimidinyl-piperazine-carboxamide structure. The final model obtained was extensively validated (q2 = 0.734; r2test = 0.966; r2m = 0.723), and based on the information derived from the contour maps we reported a series of 10 new compounds designed as powerful FAAH inhibitors (pIC50 of the best-proposed compounds = 12.196; 12.416).
ARTICLE | doi:10.20944/preprints201808.0451.v1
Subject: Chemistry, Analytical Chemistry Keywords: bone marrow oil; unsaturated fatty acid; urea inclusion; low temperature crystallization; GC/MS
Online: 27 August 2018 (11:02:38 CEST)
In this study, four kinds of animal bone marrow powders were extracted with n-hexane using the Soxhlet extraction method. Polyunsaturated fatty acids were enriched by urea inclusion and low temperature crystallization method, then were further evaluated antioxidant and antibacterial activities. These results showed that the oil composition of the n-hexane extracts of four kinds of animal bone marrow primarily consisted of palmitic acid (18.57–31.01%), stearic acid (3.6–20.95%), and oleic acid (40.22–58.69%). The ratios of saturated fatty acids (SFA)/unsaturated fatty acids (UFA) were 1/1.417, 1/1.327, 1/2.140, and 1.285/1 for sheep, bovine, horse, and camel bone marrow oil, respectively. The SFA/UFA ratios determined by the urea inclusion method were 1/1.518, 1/1.390, 1/2.037, and 1.216/1, respectively. The SFA/UFA ratios according to the low temperature crystallization method with acetone were 1/1.920, 1/2.141, 1/2.360, and 1/1.157 for sheep, bovine, horse, and camel bone marrow oil, respectively. These enrichment methods effected the concentrations of UFAs from the camel bone marrow oil. Among the methods, the low temperature crystallization method effectively enriched the UFAs. All four bone marrow oils exhibited strong antioxidant and antimicrobial activities. The horse bone marrow oil showed the strongest antioxidant activity. Both antioxidant and antimicrobial activity improved after enrichment of the UFAs. These results lay a theoretical basis for application bone marrow oil resources in food and medicine.
ARTICLE | doi:10.20944/preprints202301.0011.v1
Subject: Chemistry, Organic Chemistry Keywords: ultraviolet shield; protocell; fatty acid vesicles; origin of life; dissipative structuring; prebiotic chemistry; abiogenesis; non-equilibrium thermodynamics; thermodynamic dissipation theory; Mie scattering.
Online: 3 January 2023 (07:34:19 CET)
Theories on life’s origin generally acknowledge the advantage of a semi-permeable vesicle (protocell) for enhancing the chemical reaction-diffusion processes involved in abiogenesis. However, more and more evidence indicates that the origin of life concerned the photo-chemical dissipative structuring of the fundamental molecules under UV-C light. In this paper, we analyze the Mie UV scattering properties of such a vesicle made from long chain fatty acids. We find that the vesicle could have provided early life with a shield from the faint, but dangerous, hard UV-C ionizing light (180-210 nm) that probably bathed Earth’s surface from before the origin of life and until perhaps 1,500 million years after, until the formation of a protective ozone layer as a result of the evolution of oxygenic photosynthesis.
ARTICLE | doi:10.20944/preprints201809.0271.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Biomarkers; dietary total fat; pentadecanoic acid; 15:0; heptadecanoic acid; 17:0; odd chain fatty acids.
Online: 15 September 2018 (17:49:08 CEST)
Pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) have been described as dietary biomarkers of dairy-fat consumption with varying degrees of reliability between studies. It remains unclear how the total amount of dietary fat; one of the main confounding factors in these biomarker investigations, affects C15:0 and C17:0 circulating compositions independently to their relative intake. Additionally, it is unknown how changes in the dietary total-fat affects other fatty acids in circulation. Through two dietary studies with different total-fat levels but maintaining individual fatty acid compositions we were able to see how the dietary total-fat affects the fatty acids in circulation. We saw that there was a significant, proportionate, and robust decrease in the endogenous C15:0 levels with an increase in dietary total-fat. However, there was an increase in the circulating C17:0 compositions as the total-fat increased. To conclude, the dietary total-fat content and fat-type have a very complex influence on the relative compositions of circulating fatty acids, which are independent to the actual dietary fatty acid composition. Knowing how to manipulate circulating C15:0 and C17:0 composition is far-reaching in nutritional/pathological research as they highlight a dietary route to attenuate the development of metabolic disease (both by reducing risk and improving prognosis).
ARTICLE | doi:10.20944/preprints202112.0267.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: docosahexaenoic acid (DHA) deficiency; mitochondrial function; polyunsaturated fatty acids; membrane permeabilization; oxidative damage markers; adenine nucleotide translocase
Online: 16 December 2021 (10:57:36 CET)
The fatty acid elongase ELOngation of Very-Long-chain fatty acids protein 2 (ELOVL2) controls the elongation of polyunsaturated fatty acids (PUFA) producing precursors for omega-3, do-cosahexaenoic acid (DHA), and omega-6, docosapentaenoic acid (DPAn6) in-vivo. Expectedly, Elovl2-ablation drastically reduced the DHA and DPAn6 in liver mitochondrial membranes. Unexpectedly, however, total PUFAs levels decreased further than could be explained by Elovl2 ablation. The lipid peroxidation process was not involved in PUFAs reduction since malondial-dehyde-lysine (MDAL) and other oxidative stress biomarkers were not enhanced. The content of mitochondrial respiratory chain proteins remained unchanged. Still, membrane remodeling was associated with high voltage-dependent anion channel (VDAC) and adenine nucleotide trans-locase 2 (ANT2), a possible reflection of the increased demand on phospholipid transport to the mitochondria. Mitochondrial function was impaired despite preserved content of the respiratory chain proteins and the absence of oxidative damage. Oligomycin-insensitive oxygen consumption increased, and coefficients of respiratory control were reduced by 50%. The mitochondria became very sensitive to fatty acid-induced uncoupling and permeabilization, where ANT2 is involved. Mitochondrial volume and number of peroxisomes increased as revealed by transmission elec-tron microscopy. In conclusion, the results imply that endogenous DHA production is vital for the normal function of mouse liver mitochondria and could be relevant not only for mice but also for human metabolism.
ARTICLE | doi:10.20944/preprints202101.0186.v1
Subject: Life Sciences, Biochemistry Keywords: Docosahexaenoic acid (DHA); long chain omega-3 fatty acids; maternal supplementation; pregnancy outcomes; anthropometry; birth weight; birth length; head circumference
Online: 11 January 2021 (11:38:57 CET)
Long-chain omega-3 fatty acid status during pregnancy may influence newborn anthropometry and duration of gestation. Evidence from high-quality trials from LMICs is limited. We conducted a double-blind, randomized, placebo-controlled trial among 957 pregnant women (singleton gestation, 14-20 weeks’ gestation at enrollment) in India to test the effectiveness of 400 mg/d algal docosahexaenoic acid (DHA) compared to placebo provided from enrollment through delivery. Among 3379 women who were screened, 1171 were found eligible; 957 enrolled and were randomized. The intervention was two microencapsulated algal DHA (200 X 2= 400 mg/d) or two microencapsulated soy and corn oil placebo tablets to be consumed daily from enrollment (20 weeks) through delivery. The primary outcome was newborn anthropometry (birth weight, length, head circumference). Secondary outcomes were gestational age and 1 and 5 min Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score. The groups (DHA; n=478 and placebo; n=479) were well balanced at baseline. There were 902 live births. Compliance with the intervention was similar across groups (DHA: 88.5%; placebo: 87.1%). There were no significant differences between DHA and placebo group for birth weight (2750.6 ± 421.5 vs. 2768.2 ± 436.6 g, p=0.54), length (47.3 ± 2.0 vs. 47.5 ±2.0 cm, p=0.13) or head circumference (33.7 ± 1.4 vs 33.8 ± 1.4 cm, p=0.15). The mean gestational age at delivery was similar between groups (DHA: 38.8 ± 1.7 placebo: 38.8 ± 1.7 wk, p= 0.54) as were APGAR scores at 1 and 5 min. Supplementing mothers through pregnancy with 400mg/d DHA did not impact the offspring birthweight, length or head circumference.
ARTICLE | doi:10.20944/preprints202108.0198.v1
Subject: Biology, Animal Sciences & Zoology Keywords: depolymerizing enzyme; debranching enzyme; xylanase; arabinofuranosidase; feruloyl esterase; arabinoxylan; digestion; growth performance; volatile fatty acid; piglet
Online: 9 August 2021 (14:56:56 CEST)
This study was aimed to investigate the effect of xylan depolymerizing enzyme namely endo-xylanase (Xyn) combined with debranching enzymes namely arabinofuranosidase (Afd) and feruloyl esterase (FE) on digestion, growth performance and intestinal volatile fatty acid profile of piglets. The in vitro experiments were firstly conducted to examine the enzymological properties of Xyn, Afd and FE, the synergy among these enzymes, together with the effect of combination of these enzymes on digestion of piglet diet. The in vivo experiment was then implemented by allocating 270 35-d-old postweaning piglets into 3 treatment groups: control group, Xyn group and (Xyn+Afd+FE) group. Each group had 6 replicates (15 piglets/replicate). The results revealed a satisfying thermostability and pH stability of Xyn, Afd and FE. Combination of Xyn, Afd and FE had a superiority (P < 0.05) over Xyn alone and its combination with Afd or FE in promoting degradation of different bran fibers rich in arabinoxylan (Abx). Treatment with combination of Xyn, Afd and FE had advantages over Xyn alone to induce increasing trends (P < 0.10) of in vitro digestibility of dietary nutrients (dry matter, crude protein, crude ash and gross energy) and piglet growth performance (average daily gain, final body weight and feed efficiency), concurrent with a reduction (P < 0.05) of diarrhea rate and increases (P < 0.05) in cecal acetic acid, butyric acid and total volatile fatty acids concentrations as well as pH value of piglets. Collectively, combination of Xyn, Afd and FE was efficient in benefiting degradation of Abx in brans, as well as improving digestion, growth performance and intestinal volatile fatty acid profile of piglets.
REVIEW | doi:10.20944/preprints201906.0118.v1
Subject: Chemistry, General & Theoretical Chemistry Keywords: beef tallow biodiesel; fatty acid esters; atomic charge; molecular dipole moment; HOMO-LUMO energy gap; electrostatic potential
Online: 13 June 2019 (09:37:39 CEST)
This study deals with computational analysis of dominant fatty acid ethyl esters characterized from the biodiesel produced from waste beef tallow by means of KOH catalyzed ethanol based transesterification. Ethyl palmitate, Ethyl Oleate, Ethyl Stearate and Ethyl Myristate were identified as dominant fatty acid esters and were computed for molecular analysis in Gaussian 09 software using Density Functional Theory (B3LYP method) with 6-31G* as basis set. Geometric parameters were in accordance with existing experimental values and population analysis exhibited negative charge for oxygen atoms, both positive & negative charge for carbon atoms in all ester molecules. The molecular dipole moment was higher for unsaturated ester molecule and quadruple moment proposed electronic dislocation in X+Y direction. Also, energy gap decreased slightly with increasing carbon chain but reduced drastically with increase in unsaturation. Electrostatic potential mapping displayed negative electrostatic potential for oxygen atoms in ester linkage of all ester molecules.
ARTICLE | doi:10.20944/preprints202001.0182.v1
Subject: Chemistry, Medicinal Chemistry Keywords: dinoflagellate; Karenia mikimotoi; glycolipids; monogalactosyldiacylglycerol; monogalactosylmonoacylglycerol; polyunsaturated fatty acid methyl ester; Staphylococcus aureus; Escherichia coli; Candida albicans; anti-inflammatory activity
Online: 17 January 2020 (09:18:08 CET)
A New monogalactosyldiacylglycerol (MGDG), a known monogalactosylmonoacylglycerol (MGMG) and a known polyunsaturated fatty acid methyl ester (PUFAME) were isolated from the marine dinoflagellate Karenia mikimotoi. The planar structure of the glycolipids was elucidated using MS and NMR spectroscopic analyses and comparisons to the known glycolipid to confirm its structure. The isolation of PUFAME strongly supports the polyunsaturated fatty acid fragment of these glycolipids. The relative configuration of the sugar was deduced by comparisons of 3JHH values and proton chemical shifts with those of known glycolipids. All isolated compounds MGDG, MGMG and PUFAME (1-3) were evaluated for their antimicrobial and anti-inflammatory activity. All compounds modulated macrophage responses, with compound 3 exhibiting the greatest anti-inflammatory activity.
ARTICLE | doi:10.20944/preprints202012.0635.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Free fatty acid receptor 2; microbiota; metabolite; sensor; G-coupled protein receptor; signaling; Alzheimer’s disease; senescence; C. elegans
Online: 24 December 2020 (14:56:00 CET)
Gut microbiota and its metabolites like short chain fatty acids (SCFAs) are linked with pathology of Alzheimer’s disease (AD)- a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from SCFAs produced by microbiota in the gut. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aβ) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists, using in-silico library of more than 144,000 natural compounds, and 15 compounds were selected based on binding with FFAR2 agonist sites. Further, cell culture toxicity and FFAR2 stimulatory experiments demonstrated that Fenchol (a natural compound commonly present in basil) was potent FFAR2 agonist in neuronal cells. Interestingly, we also demonstrated that Fenchol protects Aβ-stimulated neurodegeneration in FFAR2 dependent manner. In addition, Fenchol reduced AD like phenotypes such as Aβ-accumulation and, learning and memory behaviors in Caenorhabditis (C.) elegans. Fenchol increased Aβ-clearance by increasing proteasome/lysosome activity and reduced senescence in neuronal cells. These results demonstrated that the inhibition of FFAR2 signaling promotes Aβ-induced neurodegeneration, while activating it by Fenchol as a natural agonist reverse it by promoting Aβ-clearance and reducing cellular senescence; thus stimulation of FFAR2 signaling can be a therapeutic approach to prevent/ treat AD.
ARTICLE | doi:10.20944/preprints202202.0265.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: adult neurogenesis; dentate gyrus; diet; microglia; bacterial endotoxin lipopolysaccharide; LPS; Omega 3; polyunsaturated fatty acids; sexual dimorphism; systemic inflammation
Online: 22 February 2022 (09:44:55 CET)
Maternal intake of the polyunsaturated fatty acids omega-3 (n-3 PUFA) and omega-6 (n-6 PUFA) impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). n-3 PUFA and n-6 PUFA are precursors of inflammatory regulators that potentially affect AHN and glia. Additionally, n-3 PUFA dietary supplementation may present a sexually dimorphic action in the brain. Therefore, we postulated that dietary n-6/n-3 PUFA balance shapes the adult DG in a sex-dependent manner influencing AHN and glia. We test our hypothesis by feeding adult female and male mice with n-3 PUFA balanced or deficient diets. To analyze the immunomodulatory potential of the diets, we injected mice with the bacterial endotoxin lipopolysaccharide (LPS). LPS reduced neuroblast number, and its effect was exacerbated by the n-3 PUFA deficient diet. The n-3 PUFA deficient diet reduced the DG volume, AHN, microglia number and surveilled volume. Diet effect on most mature neuroblasts was exclusively significant in female mice. Colocalization and multivariate analysis revealed an association between microglia and AHN, and the sexual dimorphic effect of diet. Our study reveals that female mice are more susceptible than males to the effect of dietary n-6/n-3 PUFA ratio on AHN and microglia.
ARTICLE | doi:10.20944/preprints202201.0013.v1
Subject: Chemistry, Applied Chemistry Keywords: hydrophilic sulfonated silica catalyst; Aliquat 336; tetrabutylammonium tetrafluoroborate; transesterification; fatty acid methyl esters, DMSO.
Online: 4 January 2022 (15:24:55 CET)
Triglycerides of waste cooking oil reacted with methanol in refluxing toluene to yield mixtures of diglycerides, monoglycerides and fatty acid methyl esters (FAMEs) in the presence of 20% (w/w) catalyst/oil using the hydrophilic sulfonated silica (SiO2-SO3H) catalyst alone or with the addition of 10% (w/w) co-catalyst/oil [(Bun4N)](BF4) or Aliquat 336]. The addition of the ammonium salts to the catalyst lead to a decrease in the amounts of diglycerides in the products, but the concentrations of monoglycerides increased. Mixtures of [(Bun4N)](BF4)/catalyst were superior to catalyst alone or Aliquat 336/catalyst for promoting the production of mixtures with high concentrations of FAMEs. The same experiments were repeated using DMSO as the solvent. The use of the more polar solvent resulted in excellent conversion of the triglycerides to FAME esters with all three-catalyst media. A simplified mechanism is presented to account for the experimental results.
ARTICLE | doi:10.20944/preprints202107.0526.v1
Subject: Life Sciences, Biochemistry Keywords: maternal pre-gestational obesity; placenta; lipid metabolism; fatty acid transporter proteins; isoprostanoids; neuroprostanes; isoprostanes; docosahexaenoic acid; arachidonic acid
Online: 23 July 2021 (08:04:47 CEST)
The rise in prevalence of obesity in women of reproductive age in both developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health, contributing to substantial economic burden on society. Placental lipid metabolism might be disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism and handling from women with pre-gestational obesity as a sole pregnancy complication and compared to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidized products of docosahexahenoic acid (DHA), neuroprostanes, and arachidonic acid (AA), isoprostanes. Placental fatty acid transporters FABP1, FABP3 and endothelial lipase protein were measured. Despite no signs of overall alterations in lipid content, increased contents of DHA, AA, DHA-derived neuroprostanes and AA-derived isoprostanes and decreased content of FABP1 protein were found in placentas from obese women. Multivariate analyses suggested that these oxidised fatty acids are associated with maternal and placental inflammation and also with birth weight. These results might shed light on the molecular mechanisms associated with altered fatty acid metabolism and lipid handling in maternal pre-gestational obesity, placing these oxidized fatty acids as novel mediators of placental function.
ARTICLE | doi:10.20944/preprints202007.0543.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: nonalcoholic fatty liver disease; lean nonalcoholic fatty liver disease; visceral fat; non-obese; fatty liver; insulin resistance
Online: 23 July 2020 (09:38:15 CEST)
Asians are known to more likely than Westerners develop fatty liver and lifestyle-related diseases despite their weight. However, the relationship between fat accumulation and lifestyle-related diseases in non-obese Asians is unknown. Therefore, this study aimed to analyze visceral fat and hepatic fat in participants with a normal body mass index (BMI) and examine their characteristics during a medical checkup. This cross-sectional study was conducted on 663 of 1,142 patients who underwent abdominal ultrasonography and who had an alcohol intake (converted to ethanol) of <30 g/day for males and <20 g/day for females and a BMI of <25 kg/m2 during a health checkup. Participants were classified into four groups: group A, visceral fat accumulation (VFA) (−) and fatty liver (FL) (−) (n = 549); group B, VFA (+) and FL(−) (n = 32); group C, VFA (−) and FL (+) (n = 58); and group D, VFA (+) and FL (+) (n = 24). The frequencies of lifestyle-related disease complications, liver function tests, and liver fibrosis were evaluated among the four groups. Compared with group A (control), groups B, C, and D had higher number of males; BMI; abdominal circumference, ALT, AST, γ-GTP, triglyceride, uric acid, fasting blood sugar levels; and incidence of hyperlipidemia. Groups C and D had higher ALT, HbA1c, cholinesterase, and triglyceride levels; FIB4 index; and number of patients with diabetes mellitus (DM) than groups A and B; however, there was no difference between groups A and B. FL is a risk factor of DM and liver fibrosis in non-obese Japanese individuals; however, VFA only is not a risk factor of DM and liver fibrosis.
ARTICLE | doi:10.20944/preprints201701.0093.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: 22:6 docosahexaenoic acid; ω-3 fatty acids; offspring of obese mothers; offspring of lean mothers; insulin-dependent skeletal muscle glucose uptake
Online: 20 January 2017 (04:59:25 CET)
Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.
ARTICLE | doi:10.20944/preprints202008.0228.v3
Subject: Medicine & Pharmacology, Pediatrics Keywords: Trans fatty acids; saturated fatty acids; ultra-processed foods; children; Tunisia
Online: 4 November 2021 (11:26:56 CET)
Excessive intake of fat and fatty acids is associated with major health hazards such as obesity or chronic diseases. The aim of this study was to provide the first data on total fat, saturated fatty acids (SFA) and trans fatty acids (TFA) intakes and their major food sources in Tunisian children. A total of 1200 children, aged 3 to 9 years old (yo), were randomly selected from primary schools and kindergarten under a cross-sectional design. The 24-hour recall method and food frequency questionnaire were used to assess dietary intake. The energy percentages of total fat, SFA and TFA in Tunisian children were respectively 29.6, 11.4 and 0.15. No sex differences were found. The WHO recommendations for total fat, SFA and TFA were adopted by 58 %, 39 % and 89 % of the study population, respectively. The leading food groups of fat and fatty acids were ultra-processed foods, breakfast cereals and dairy products. The meat, fish, eggs and fish alternatives were the fifth main contributors to the total fat and SFA intakes in Tunisian children. The implementation of a relevant strategy for fat reduction, especially from ultra-processed foods, considered as low nutrient energy-dense products, is needed to promote health among children and prevent diet-related chronic diseases.
REVIEW | doi:10.20944/preprints201705.0135.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: dietary substitution; CVD; saturated fatty acids; protein; monounsaturated fatty acids; polyunsaturated fatty acids; dairy fat; refined carbohydrates; whole grains
Online: 18 May 2017 (04:01:53 CEST)
Dietary recommendations to decrease the risk of cardiovascular disease (CVD) have focused on reducing intake of saturated fatty acids (SFA) for more than 50 years. While the 2015-2020 Dietary Guidelines for Americans advise substituting both monounsaturated and polyunsaturated fatty acids for SFA, evidence supports other nutrient substitutions that will also reduce CVD risk. For example, replacing SFA with whole grains, but not refined carbohydrates, reduces CVD risk. Replacing SFA with protein, especially plant protein may also reduce CVD risk. While dairy fat (milk, cheese) is associated with a slightly lower CVD risk compared to meat, dairy fat results in a significantly greater CVD risk relative to unsaturated fatty acids. As research continues, we will refine our understanding of dietary patterns associated with lower CVD risk.
ARTICLE | doi:10.20944/preprints201806.0119.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: preterm infant; enteral nutrition; lipids; omega-3 fatty acids; omega-6 fatty acids; Docosahexaenoic acid; Arachidonic acid; long-chain polyunsaturated fatty acids.
Online: 7 June 2018 (11:34:53 CEST)
Human milk fat is a concentrated source of energy and provides essential and long chain polyunsaturated fatty acids. According to previous experiments, human milk fat is partially lost during continuous enteral nutrition. However, these experiments were done over relatively short infusion times, and a complete profile of the lost fatty acids was never measured. Whether this lost happens considering longer infusion times or if some fatty acids are lost more than others remain unknown. Pooled breast milk was infused through a feeding tube by a peristaltic pump over a period of 30 minutes and 4, 12 and 24 hours at 2 ml/hour. Adsorbed fat was extracted from the tubes, and the fatty acid composition was analyzed by Gas chromatography-mass spectrometry. Total fat loss (average fatty acid loss) after 24 hours was 0.6 ± 0.1%. Short-medium chain (0.7%, p=0.15), long chain (0.6%, p=0.56) saturated (0.7%, p=0.4), monounsaturated (0.5%, p=0.15), polyunsaturated fatty (0.7%, p=0.15), linoleic (0.7%, p=0.25), and docosahexaenoic acids (0.6%, p=0.56) were not selectively adsorbed to the tube. However, very long chain fatty (0.9%, p=0.04), alpha-linolenic (1.6%, p=0.02) and arachidonic acids (1%, p=0.02) were selectively adsorbed and therefore lost in a greater proportion than other fatty acids. In all cases, the magnitude of the loss was clinically low.
ARTICLE | doi:10.20944/preprints202002.0284.v1
Online: 20 February 2020 (05:27:15 CET)
Wild game consumption has been associated with health benefits, but the influence on protein metabolism remains unknown. We compared the feeding-induced response to 2 oz of free-range reindeer (FR) versus commercial beef (CB) using stable isotope methodology. Seven male and female participants (age: 38±12 years; body mass index: 24±3 kg/m2) completed two studies using a randomized, crossover design in which they ingested 2 oz of FR or CB. L-[ring 2H5]phenylalanine & L-[ring 2H2]tyrosine were delivered via primed, continuous intravenous infusion. Blood samples were collected during the basal period and following consumption of FR or CB. Feeding-induced changes in whole body protein synthesis (PS), protein breakdown (PB), and net protein balance (NB) were determined via analysis of plasma samples for phenyalanine and tyrosine enrichment by gas chromatography mass spectrometry; plasma essential amino acid concentrations were determined by liquid chromatography-electrospray ionization-mass spectrometry. Plasma post-prandial essential amino acid (EAA) concentrations were higher with the ingestion of FR compared to CB (P=0.02). The acute feeding-induced response in PS was not different in either trial, but PB was reduced with the ingestion of FR compared to CB (P<0.0001). The difference in PB contributed to a superior level of NB (P<0.0001). When protein kinetics were normalized relative to the amino acids ingested, PB/EAAs and total amino acids ingested were reduced (P<0.01 and 0.001, respectively) in FR compared to CB; contributing to greater NB/total amino acid ingested (P<0.0001) between FR and CB. We conclude that the nutrient profiles of FR may have a more favorable benefit on protein metabolism compared to CB. These data support the potential health benefits of wild game in the preservation of whole-body protein.
REVIEW | doi:10.20944/preprints202108.0147.v1
Subject: Medicine & Pharmacology, Allergology Keywords: metabolic syndrome; colorectal cancer; nonalcoholic fatty liver disease; liver surgery; hepatic resection; fatty liver; nutrition; protein
Online: 5 August 2021 (14:55:25 CEST)
Over the recent years, non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in the developed world, accounting for 20% to 46% of liver abnormalities. Steatosis is the hallmark of NAFLD and is recognized as an important risk factor for complication and death after general surgery, and even more so after liver resection. Similarly, liver steatosis also impacts the safety of live liver donation and transplantation. We aim to review surgical outcomes after liver resection for colorectal-metastases in patients with steatosis, and discuss the most common pre-operative strategies to reduce steatosis. Finally, as illustration, we report the favourable effect of a low-caloric, hyper-protein diet during a two-stage liver resection for colorectal metastases in a patient with severe steatosis.
ARTICLE | doi:10.20944/preprints201811.0237.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: epidemiology; prospective cohort study; n-6 fatty acids; n-3 fatty acids; linoleic acid; arachidonic acid
Online: 9 November 2018 (04:07:36 CET)
Background: The prognostic value of erythrocyte levels of the n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. Methods: We examined CV outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as a function of baseline levels of different length n-6 FAs (18 carbon, 20 carbon and 22 carbon) in the erythrocyte membranes. Clinical outcomes were monitored for up to 9.5 years (median follow up, 7.26 years). Cox proportional hazards models were adjusted for a variety of demographic characteristics, clinical status and RBC n-6 and long chain n-3 FA content. Results: There were 245 CV events, 119 CHD events, 105 ischemic strokes, 58 CVD deaths, and 350 deaths from all causes. Few associations between either mortality or CVD outcomes were observed for the n-6 FAs, with those that were observed becoming non-significant after adjusting for n-3 FA levels. Conclusions: Higher circulating levels of the marine n-3 FA levels are associated with reduced risk for incident CVD and ischemic stroke and for death from CHD and all-causes, however in the same sample, little evidence exists for association with n-6 FAs. Further work is needed to identify a full profile of FAs associated with cardiovascular risk and mortality.
ARTICLE | doi:10.20944/preprints202203.0120.v1
Subject: Biology, Animal Sciences & Zoology Keywords: magnesium; absorption; rumen; butyrate; volatile fatty acids
Online: 8 March 2022 (08:59:14 CET)
The aim of the present study was to measure the apparent absorption of magnesium (Mg) originating from Mg-butyrate. Six mid-lactation Holstein Friesian dairy cows were used with dietary treatments arranged in a cross-over design. Two different diets were fed during the experiment, consisting of a low Mg diet without Mg-butyrate (L-Mg, 3.1g Mg/kg dry matter) or a high Mg diet with Mg-butyrate (H-Mg, 3.9 g Mg/kg dry matter). Cows offered the L-Mg diet ingested 54.7 g Mg/day while the cows fed the H-Mg diets ingested 66.3 g Mg/day (P < 0.001). The fecal excretion of Mg, however, was similar between the two experimental diets (P = 0.174). Consequently, apparent Mg absorption was found to be 7.9 percentage units greater (P = 0.038) when the cows were fed the diet supplemented with Mg-butyrate. The greater Mg absorption after feeding the H-Mg diet was, however, not reflected by a greater urinary Mg concentration (P = 0.228). These results indicate that the availability of Mg from the Mg-butyrate supplemented diet is high (34.1% of intake). The fractional Mg absorption from Mg-butyrate was calculated to be 71.6%. In conclusion, Mg-butyrate is an attractive alternative to supplement dairy rations with Mg.
ARTICLE | doi:10.20944/preprints201704.0144.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: alcoholic fatty liver disease; PARP; PJ34; triglyceride
Online: 24 April 2017 (05:30:53 CEST)
The specific role of nicotinamide adenine dinucleotide (NAD) in hepatic triglyceride (TG) accumulation in alcoholic fatty liver disease (AFLD) were unclear. Poly ADP ribose polymerase (PARP) is a NAD-consuming enzyme and its specific role in the pathogenesis of AFLD is still elusive. In current investigation, we found that chronic alcohol exposure enhanced hepatic PARP expression and activity and lowered hepatic NAD+ level. PARP activity inhibitor PJ34 decreased the intracellular TG content in hepatocyte. Moreover, PJ34 suppressed the gene expression of DGAT1 and DGAT2 and elevated the intracellular NAD+ level in hepatocyte. These mechanistic observation was validated in alcohol-fed mice injected with PJ34 intraperitoneally. PJ34 injection attenuated hepatic TG accumulation in alcohol-fed mice. Further, the gene expression of hepatic SERBP-1c, DGAT1 and DGAT2 were lowered by PJ34 injection, while the hepatic NAD+ level was augmented by PJ34 injection in alcohol-fed mice. At last, the nicotinamide riboside supplementation alleviated hepatic TG accumulation in alcohol-fed mice. These data indicate that applying PARP specific inhibitor PJ34 by intraperitoneal injection attenuated hepatic NAD+ depletion and TG accumulation in alcohol-fed mice, which might be a potential candidate for AFLD therapy.
ARTICLE | doi:10.20944/preprints201610.0090.v1
Subject: Chemistry, Analytical Chemistry Keywords: Laminaria hyperborean; lipids; fatty acids; GC-MS
Online: 21 October 2016 (08:59:13 CEST)
A thorough analysis and comparison of the fatty acid profiles of stipe and blade from Laminaria hyperborea, a kelp species found in the northern Atlantic, is presented. Lipids were extracted and fractionated into neutral lipids, free fatty acids and polar lipids, then derivatized to fatty acid methyl esters prior to GC-MS analysis. A total of 42 fatty acids were identified and quantified, including the n-3 fatty acids α-linolenic acid, stearidonic acid and eicosapentaenoic acid. An n-6/n-3 ratio of 0.8:1 was found in blade and 3.5:1 in stipe, respectively. The ratios vary between the lipid fractions within stipe and blade, with the lowest ratio in the polar lipid fraction of blade. The fatty acid amounts are higher in blade than in stipe, and the highest amounts of n-3 fatty acids are found within the neutral lipid fractions. The amounts of polyunsaturated fatty acids are 3.4 times higher in blade than stipe. This study highlights the compositional differences between the lipid fractions of stipe and blade from L. hyperborea. The amount of polyunsaturated fatty acids, compared to saturated- and monounsaturated fatty acids, as well as the n-6/n-3-ratio, is known to influence human health. In the pharmaceutical, food, and feed industries this can be of importance for production and sale of different health products. Additionally, lipids are today among the unused by products of alginate production, exploiting this material for commercial interest should give both economical and environmental benefits.
ARTICLE | doi:10.20944/preprints202009.0241.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: prebiotic; oligosaccharides; gut microbiota; fatty liver; metabolism; mitochondria
Online: 11 September 2020 (04:17:52 CEST)
Understanding the importance of gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat associated with low abundance of Faecalibacterium prausnitzii in humans and further, administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed to target F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD) or low (LFD) fat-diet for 12-weeks in Wistar rats (n=10/group). XOS increased F. prausnitzii growth having only minor impact on the GM composition. When supplemented with HFD, XOS prevented hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. 1H-NMR analysis of caecal metabolites showed that compared to HFD, LFD group had healthier caecal short-chain fatty acid profile and the combination of HFD and XOS was associated with reduced caecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Caecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, our study identifies F. prausnitzii as a possible target to treat NAFLD with XOS. The underlying preventive mechanisms involved improved hepatic oxidative metabolism.
ARTICLE | doi:10.20944/preprints202001.0068.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: prebiotics; polyols; short chain fatty acids, Headspace Analysis
Online: 9 January 2020 (04:44:49 CET)
This pilot study of Streptococcus mutans ATCC 35668 grown in media with and without polyols (erythritol) measured the resultant metabolites, including the short chain fatty acids by using head space analysis. Brain Heart Infusion Broth (BHI2 or BHI10) supplemented with 2% or 10% sucrose containing no polyols or either erythritol or xylitol and Streptococcus mutans (ATCC 35668) was grown aerobically. After 48 hours of growth the supernatant were harvested and centrifuged to pellet bacteria. Supernatants were removed from bacterial pellets then submitted for Short Chain Fatty Acid (SCFA) analysis with an Agilent Technologies (Santa Clara, CA 95051) system configured from three components, a 5973 mass selective detector, a 6890N gas chromatographer, and a 7697A headspace sampler. Streptococcus mutans growing in Brain Heart Infusion Broth (BHI2 or BHI10) supplemented with 2% or 10% sucrose but containing no polyols produced the following short chain fatty acids: methyl isovalerate, acetic acid, propionic acid, butanoic acid, pentanoic acid, ethyl butaric acid, 4-methylvaleric acid, hexanoic acid. When the Brain Heart Infusion Broth (BHI2 or BHI10) supplemented with 2% or 10% sucrose containing erythritol was used as media for this Streptococcus mutans strain, the following were produced: ethanol, acetoin, and acetic acid. Our results would suggest that constituents of the media may affect the bacterial metabolite production.
ARTICLE | doi:10.20944/preprints201809.0505.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: renewable energy, microwave, free fatty acid, crude oil
Online: 26 September 2018 (10:31:20 CEST)
A novel method proposed in the production of Calophyllum inophyllum biodiesel has been investigated experimentally. In this study, we report the results of biodiesel processing with electromagnetic induction technology. The method used is to compare the results of Calophyllum inophyllum biodiesel processing between conventional, microwave and electromagnetic induction. The degumming, transesterification, and esterification process of the 3 methods are measured by stopwatch to obtain time comparison data. Characteristics of viscosity, density, and Fatty Acid Metil Ester (FAME) were obtained from testing of a Gas Chromatography-mass Spectrometry (GCMS) at the Polytechnic Chemistry Laboratory of the State of Malang. The results show that the biodiesel produced by this method satisfies the biodiesel standards and their characteristics are better than the biodiesel produced by conventional and microwave methods. The electromagnetic induction method also offers a fast and easy route to produce biodiesel with the advantage of increasing the reaction rate and improving the separation process compared to other methods. This advanced technology has the potential to significantly increase biodiesel production with considerable potential to reduce production time and costs.
BRIEF REPORT | doi:10.20944/preprints201801.0286.v1
Subject: Biology, Entomology Keywords: volatile fatty acids; Alphitobius diaperinus; locomotor activity; repellency
Online: 30 January 2018 (14:46:51 CET)
Volatile fatty acids (VFAs) are a group of common metabolites with a potential of universal infochemicals dedicated to transferring of information between higher organisms and bacteria either from microbiome or external environment. VFAs are common substances among various insect orders, there are numerous studies exploring their influence on the behavior of different insect species. In relation to papers published by J. E. McFarlane, we assess the effects of formic, acetic, propionic, butyric, valeric acids on spatial preference of common stored food grain products, and poultry industry pest – lesser mealworm (Alphitobius diaperinus). We present novel method of continuous, simultaneous assessment of site preference as well as travelled distance in constant-flow olfactometer. All tested VFAs except valeric had a significant repellent effect with formic acid being effective in the lowest concentration. Additionally, VFAs significantly altered distance travelled by insects. Obtained results indicate a potential role of VFAs in the olfactory guided behavior of A. diaperinus, we speculate that reaction to the presence if VFAs may deviate form specificity of species’ original habitat.
REVIEW | doi:10.20944/preprints202208.0468.v1
Subject: Biology, Physiology Keywords: esculetin; cancer; oxidative stress; inflammation; arthritis; diabetes; fatty liver
Online: 29 August 2022 (05:25:05 CEST)
Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as Sonchus grandifolius, Aesculus turbinata, and many others. Glycosides and caffeic acid conjugates are the common forms of esculetin present in medicinal plants. Esculetin acts as an antioxidant, anti-inflammatory, anti-diabetic, anti-hepatic, and anti-cancer agent by inhibiting the production of free radicals, inflammatory mediators, and genes that cause liver diseases and cancer. It also aids in the regulation of blood sugar. Scientists developing pharmaceutical formulations require some rationale and preliminary studies for drug design, but a small number of clinical studies on humans containing esculetin limit its potential for use as a safe alternative drug. Therefore, in this review article, the published studies have been reviewed to identify the pathogenesis of cancer, oxidative stress, inflammation, arthritis, diabetes and fatty liver along with the discussion on potential therapeutic strategies of esculetin. Advancements in our understanding of these diseases will aid in the development of new and innovative medications for treating many ailments. In conclusion, esculetin has immense potential to be used as a safe drug against many diseases but requires further testing and confirmation through clinical trials.
ARTICLE | doi:10.20944/preprints202202.0149.v1
Subject: Life Sciences, Molecular Biology Keywords: immune response; fatty acid; lipid metabolism; RNA-Seq; transcriptome
Online: 10 February 2022 (10:57:03 CET)
The objective of this study was to identify key transcription factors involved in lipid metabolism and immune response related to the differentially expressed genes (DEG) from the liver samples of 35 pig model for metabolic diseases fed diets containing either 1.5 or 3.0% soybean oil (SOY1.5 or SOY3.0). A total of 281 DEG between SOY1.5 and SOY3.0 diets (log2fold-change ≥ 1 or ≤ −1; FDR-corrected p-value < 0.1) were identified, in which 129 were down-regulated and 152 were up-regulated in SOY1.5 group. The functional annotation analysis detected transcription factors linked to lipid homeostasis and immune response, such as RXRA, EGFR, and SREBP2 precursor. These findings demonstrated that key transcription factors related to lipid metabolism could be modulated by dietary inclusion of soybean oil. It could contribute to nutrigenomics research field that aims to elucidate dietary interventions in animal and human health, as well as to drive the food technology and science.
ARTICLE | doi:10.20944/preprints202103.0161.v1
Subject: Life Sciences, Biochemistry Keywords: chicken eggs; quail eggs; fatty acids; iron; zinc; cholesterol
Online: 4 March 2021 (14:02:38 CET)
All over the world birds’ eggs are an important and valuable component of the human diet. The study aimed to compare the content of lipid components and their nutritional value as well as iron and zinc levels in chicken and quail eggs commonly available on the market. In egg lipids, unsaturated acids were dominated, especially oleic acid, the content of which was about 40% of total fatty acids (TFA). Linoleic acid was the major polyunsaturated fatty acid. Compared to other products of animal origin, eggs were characterized by favourable values of lipid quality indices, especially index of atherogenicity, thrombogenicity and hypocholesterolemic to hypercholesterolemic ratio. In the present study, no differences in the content of tested nutrients between eggs from different production methods (organic, free-range, barn, cages), as well as inter-breed differences were noticed. Cluster analysis showed that eggs enriched in n3 PUFA (according to producers’ declaration) differ from other groups of chicken eggs. However, only in eggs from one producer, the amount of EPA and DHA exceed 80 mg per 100 g, entitling to use the nutrition claim on the package. Quail eggs differed from chicken eggs in FA profile; they also had much higher iron and cholesterol levels.
REVIEW | doi:10.20944/preprints202101.0516.v1
Subject: Medicine & Pharmacology, Allergology Keywords: MAFLD; NAFLD; fatty liver; metabolic syndrome; obesity; children; nomenclature
Online: 25 January 2021 (15:36:49 CET)
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, which predispose to more serious hepatic conditions. It ranges from simple liver steatosis to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis and even end-stage liver disease. Since obesity became one of the most important health concerns wordwide, a considerable increase in the prevalance of NAFLD and other metabolic implications has been observed, both in adults, and children. Due to the coexistence of visceral obesity, insulin resistance, dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome (MetS). These relationship between NAFLD and MetS led to set up in adults new term combining both of these conditions, called metabolic dysfunction-associated fatty liver disease (MAFLD). Based of these findings, we propose set of criteria, which may be useful to diagnose MAFLD in children and adolescents.
ARTICLE | doi:10.20944/preprints202007.0532.v1
Subject: Biology, Other Keywords: Phosphatidylinositol; actin remodeling; phagocytosis; dietary fatty acids; Alzheimer’s disease
Online: 22 July 2020 (14:15:35 CEST)
Alzheimer’s disease is one of the neurodegenerative diseases, characterized by the accumulation of abnormal protein deposits, which disrupt the signal transduction in neurons and other glia cells. The pathological protein Tau and amyloid-β contributes to the disrupted microglial signaling pathways, actin cytoskeleton, and cellular receptor expression. The important secondary messenger lipids i.e., phosphatidylinositols are largely affected by protein deposits of amyloid-beta in Alzheimer’s disease. Phosphatidylinositols are the product of different phosphatidylinositol kinases and the state of phosphorylation at D3, D4, and D5 positions of inositol ring. PI 3, 4, 5-P3 involves in phagocytic cup formation and relates actin remodeling whereas PI 4, 5-P2-mediates the process of phagosomes formation and further fusion with early endosome. The necessary activation of actin-binding proteins such as Rac, WAVE complex, and ARP2/3 complex for the actin polymerization in the process of phagocytosis, migration is regulated and maintained by PI 3, 4, 5-P3 and PI 4, 5-P2. Dietary fatty acids depending on their ratio and types of intake influence secondary lipid messenger along with the cellular content of phaphatidylcholine and phosphatidylethanolamine. The deposited Aβ deposits and extracellular Tau seed disrupt levels of phosphatidylinositol and actin cytoskeletal changes that hamper microglia signaling pathways in AD. We hypothesize that being a lipid species intracellular levels of phosphatidylinositol would be regulated by dietary fatty acids. We keen to understand different types of phosphatidylinositol species levels in signaling events such as phagocytosis and actin remodeling owing to the exposure of various types of dietary fatty acids.
ARTICLE | doi:10.20944/preprints201911.0251.v1
Subject: Life Sciences, Biotechnology Keywords: endophyte; Trichoderma; fatty acid; antifeedant, myzus persicae; culture media
Online: 21 November 2019 (15:00:33 CET)
Increasing pesticide resistance in plant pathogens is major concern in agriculture production. Research on ecofriendly alternatives of chemical pesticides are more in demand in pesticide industry. In the current study, an ethyl acetate extract from the endophytic fungus Trichoderma sp. EFI 671, isolated from the stem parts of the medicinal plant Laurus sp., was screened for bioactivity against plant pathogens (Fusarium graminearum, Rhizoctonia solani, Sclerotinia sclerotiorum and Botrytis cinerea), insect pests (Spodoptera littoralis, Myzus persicae, Rhopalosiphum padi) and plant parasites (Meloidogyne javanica). The bioactive components have been characterized following a bioassay-guided isolation against M. persicae. The chemical study of this bioactive extract resulted in the isolation of 1-oleoyl-2-linoleoyl-3-palmitoylglycerol (1), eburicol (2), (24R)-stigmast-4-ene-3-one or β-sitostenone (3), ergosterol (4) and ergosterol peroxide (5). The free fatty acids present in compound 1 (oleic, linoleic and palmitic) showed strong dose-dependent aphid antifeedant effects against M. persicae. Liquid (PDB, and SDB) and solid (corn, sorghum, pearl millet and rice) growth media were tested in order to optimize the yield and bioactivity of the fungal extracts. Pearl millet and corn gave the highest extract yields. All the extracts from these solid media had strong effects against M. persicae with sorghum being the most active. Corn increased the content in linolenic, pearl millet the oleic and stearic and sorghum oleic and linolenic acids compared to rice. Their antifeedant effects correlated with linoleic /oleic acids. The phytotoxic effects of these extracts against Lolium perenne and Lactuca sativa varied with culture media, with sorghum being the least toxic.
ARTICLE | doi:10.20944/preprints201812.0163.v1
Subject: Chemistry, Food Chemistry Keywords: authenticity; chromatographic fingerprint; fatty acids; classification; linear discriminant analysis
Online: 13 December 2018 (08:43:49 CET)
The fatty-acid profiles of five main commercial pistachio cultivars, including Ahmad-Aghaei, Akbari, Chrok, Kalle-Ghouchi and Ohadi, were determined by gas chromatography: palmitic (C16:0), palmitoleic (C16:1), stearic (C18:0), oleic (C18:1), linoleic (C18:2), linolenic (C18:3) arachidic (C20:0) and gondoic (C20:1) acid. Based on the oleic to linoleic acid (O/L) ratio, a quality index was determined for these five cultivars: Ohadi (2.40) < Ahmad-Aghaei (2.60) < Kale-Ghouchi (2.94) < Chrok (3.05) < Akbari (3.66). Principal component analysis (PCA) of the fatty-acid data yielded three significant PCs, which together account for 80.0% of the total variance in the data set. A linear discriminant analysis (LDA) model evaluated with cross validation correctly classified almost all samples: the average percent accuracy for the prediction set was 98.0%. The high predictive power for the prediction set shows the ability to indicate the cultivar of an unknown sample based on its fatty-acid chromatographic fingerprint.
ARTICLE | doi:10.20944/preprints201810.0563.v1
Subject: Life Sciences, Biochemistry Keywords: mitochondrial metabolism; aging; monoacylglyceride; polyunsaturated fatty acids; oxidative stress
Online: 24 October 2018 (09:40:31 CEST)
During the last decade, essential polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived from marine sources have been investigated as nonpharmacological dietary supplements to improve different pathological conditions, as well as aging. The aim of this study was to determine the effects of dietary n-3 PUFA monoacylglycerides (MAG, both EPA and DHA) on the mitochondrial metabolism and oxidative stress of a short-lifespan model, Drosophila melanogaster, sampled at five different ages. Our results showed that diets supplemented with MAG-EPA and MAG-DHA increased median lifespan by 14.6% and decreased mitochondrial proton leak resulting in an increase of mitochondrial coupling. The flies fed on MAG-EPA also had higher electron transport system capacity and mitochondrial oxidative capacities. Moreover, both n-3 PUFAs delayed the occurrence of lipid peroxidation, but only flies fed the MAG-EPA diet showed maintenance of superoxide dismutase activity during aging. Our study therefore highlights the potential of n-3 PUFA monoacylglycerides as nutraceutical compounds to delay the onset of senescence by acting directly or indirectly on the mitochondrial metabolism, and suggests that Drosophila could be a relevant model for the study of the fundamental mechanisms linking the effects of n-3 PUFAs to aging.
ARTICLE | doi:10.20944/preprints201808.0026.v1
Subject: Life Sciences, Other Keywords: AMPK; liver; lipid metabolism; fatty acid oxidation; indirect calorimetry
Online: 1 August 2018 (16:06:39 CEST)
The energy sensor AMP-activated protein kinase (AMPK) is a key player in the control of energy metabolism. AMPK regulates hepatic lipid metabolism through the phosphorylation of its well-recognized downstream target acetyl CoA carboxylase (ACC). Although AMPK activation is proposed to lower hepatic triglyceride (TG) content via the inhibition of ACC to cause inhibition of de novo lipogenesis and stimulation of fatty acid oxidation (FAO), its contribution to the inhibition of FAO in vivo has been recently questioned. We generated a mouse model of AMPK activation specifically in the liver achieved by expression of a constitutively active AMPK using adenoviral delivery. Indirect calorimetry studies revealed that liver-specific AMPK activation is sufficient to induce a reduction in the respiratory exchange ratio and an increase in FAO rates in vivo. This led to a more rapid metabolic switch from carbohydrate to lipid oxidation during the transition from fed to fasting. Finally, mice with chronic AMPK activation in the liver display high fat oxidation capacity evidenced by increased [C14]-palmitate oxidation and ketone body production leading to reduced hepatic TG content and body adiposity. Our findings suggest a role for hepatic AMPK in the remodeling of lipid metabolism between the liver and adipose tissue.
ARTICLE | doi:10.20944/preprints201801.0210.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: fructose; intestinal microbiota; short-chain fatty acids; metabolic profiling
Online: 23 January 2018 (05:31:27 CET)
Increased sugar intake is implicated in Type-2 diabetes and fatty liver disease. Mechanisms by which glucose and fructose components promote these conditions are unclear. We hypothesize that alterations in intestinal metabolite and microbiota profiles specific to each monosaccharide are involved. Two groups of six adult C57BL/6 mice were fed for 10-weeks with a diet where either glucose or fructose was the sole carbohydrate component (G and F, respectively). A third group was fed with normal chow (N). Fecal metabolites were profiled every 2-weeks by 1H NMR and microbial composition was analysed by real-time PCR (qPCR). Glucose tolerance was also periodically assessed. N, G and F mice had similar weight gains and glucose tolerance. Multivariate analysis of NMR profiles indicated that F mice were separated from both N and G, with decreased butyrate and glutamate and increased fructose, succinate, taurine, tyrosine and xylose. Compared to N and G, F mice showed a shift in microbe populations from gram-positive Lactobacillus spp. to gram-negative Enterobacteria species. Substitution of normal chow carbohydrate mixture by either pure glucose or fructose for 10 weeks did not alter adiposity or glucose tolerance. However, F G and N mice generated distinctive fecal metabolite signatures with incomplete fructose absorption as a dominant feature of F mice.
ARTICLE | doi:10.20944/preprints202211.0270.v1
Subject: Life Sciences, Other Keywords: type 2 diabetes mellitus; non-alcoholic fatty liver disease; dynapenia
Online: 15 November 2022 (03:23:47 CET)
Background: Dynapenia and non-alcoholic fatty liver disease (NAFLD) are common, especially in the middle and advanced-age diabetic male population. We aimed to examine the clinical features, NAFLD severity, and parameters associated with the presence of dynapenia in type 2 diabetes mellitus (T2DM) cases. Material and Methods: One hundred thirty-five male patients diagnosed with T2DM between 45 and 65 years of age were included. Patients were staged by ultrasonography according to NAFLD status. Results: There were significant differences in muscle strength, upper arm circumference, calf circumference, and up-and-go test scores between the NAFLD groups (p<0.001 for all). The frequency of dynapenia was lower, and arm and calf circumferences were higher in patients without NAFLD. The muscle strength, upper arm circumference, calf circumference, and up-and-go test scores were significantly lower in the dynapenic group compared to the non-dynapenic group (p<0.005 for all). The prevalence of dynapenia increased along with the increase in NAFLD stages (p<0.001). Conclusions: We detected a significant association between NAFLD and dynapenia in middle-aged men with T2DM. As muscle strength decreases, the amount of fat in the liver increases, and as the fat in the liver increases, muscle strength decreases.
ARTICLE | doi:10.20944/preprints202208.0395.v1
Subject: Engineering, Control & Systems Engineering Keywords: asymptotically observer; homogeneous reaction systems; anaerobic digestion; volatile fatty acids
Online: 23 August 2022 (05:18:34 CEST)
This work presents a methodology that seeks to be a new standard in modeling identification in anaerobic digestion reactors. Because it is not possible to measure all variables with reliable and cost-efficient real-time methods, a specific structure composed of an asymptotic observer for the concentration of state variables; acidogenic and methanogenic bacterias, unlock the use of new types of raw sludges for industrial control and monitoring purposes. New yield parameters were included in the reduced anaerobic digestion model (ADM2) used as the core, precisely two terms in total alkalinity, to bring about the modeling of additional organic materials at inlet containing proteins or amino acids. The fermentation of these substances introduces ammonium, providing variations in the amount of alkalinity available inside the reaction. The new model is used to solve an optimization problem that calculates the parameters that best fit the dynamics of state variables with the same information taken on the experimental data. The adjustment process started with the genetic algorithm; however, to improve the performance, a novel method is proposed called step-ahead. Together, including the design of an asymptotic observer, numerical simulations demonstrate the strengths of the structure, which constitutes a significant step in paving the way further to implement feasible, cost-effective control and monitoring systems in the industry.
REVIEW | doi:10.20944/preprints202205.0252.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: chemokine; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; inflammation; immune cells
Online: 19 May 2022 (07:51:15 CEST)
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Sustained hepatic inflammation is a key driver of the transition from simple fatty liver to nonalcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. Hepatic inflammation is orchestrated by chemokines, a family of chemoattractant cytokines, which are produced by hepatocytes, Kupffer cells (liver resident macrophages), hepatic stellate cells, endothelial cells, and vascular smooth muscle cells. Over the last three decades, accumulating evidence from both clinical and experimental investigations demonstrated that chemokines and their receptors are increased in the livers of NAFLD patients and that CC chemokine ligand (CCL) 2 and CCL5, in particular, play a pivotal role in inducing insulin resistance, steatosis, inflammation, and fibrosis in the liver disease. Cenicriviroc (CVC), a dual antagonist of these chemokine’s receptor, CCR2 and CCR5, has been tested in clinical trials in patients with NASH-associated liver fibrosis. Additionally, recent studies revealed that other chemokines, such as CCL3, CCL25, CX3C chemokine ligand 1 (CX3CL1), CXC chemokine ligand 1 (CXCL1), and CXCL16 can also contribute to the pathogenesis of NAFLD. Here, we review recent updates on the roles of chemokines in the development of NAFLD and their blockade as potential therapeutic approaches.
ARTICLE | doi:10.20944/preprints202112.0125.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: cows; milk fat; ruminal fluid; milk fatty acids; energy balance
Online: 8 December 2021 (14:08:31 CET)
The trials were performed on 20 multiparous cows of Holstein breed (39.7 ± 0.75 kg of milk) at the end of the first phase of lactation this different milk fat (4.1-2.8%). The aim of the research was to study the characteristics of nutrition, metabolism and biosynthesis of milk components in highly productive dairy cows with normal and low milk fat levels and the timing of their productive use. Study the characteristics of fermentation of scar formation substrates and their use in energy metabolism and biosynthesis of the milk components. Found that low fat milk is not associated with a lack of formation of acetate in the rumen (6.1 vs. 6.6 mmol/dl in the contents of the rumen, р>0.05) and the non change in the hormonal profile, but depends on the reduction of fatty acids synthesis de novo in mammary gland, regulated by conjugated higher fatty acids. The result is a reduction in the need of cows in the exchange energy (reduction of heat transfer by 6.2 MJ), a shorter service period (109.5 vs.139 days) and the prolongation of their productive use (the number of lactations correlated back with the level of fat in milk (r=-0.68, p<0.05, n=1300).
ARTICLE | doi:10.20944/preprints202011.0674.v1
Subject: Life Sciences, Biochemistry Keywords: chitosan; microbial synthesis; milk composition; volatile fatty acids; purine derivatives
Online: 26 November 2020 (14:15:52 CET)
The study compared the influence of chitosan sources on rumen fermentation, methane emission and milk production in lactating dairy cows fed a glycerin-based diet. Six, lactating Holstein-Frisian crossbreeds (410 ± 5.0 kg BW, 120 ± 21 day-in-milk), were arranged in a 3 x 3 replicated Latin square design. In addition to control, a 2% chitosan extract supplement and a 2% commercial chitosan supplement of dry matter intake were the treatments. The results denoted that no significant differences on daily dry matter, nutrients or estimated energy intake were noted when cows received different sources of chitosan. Nutrient digestibility was not influenced differently by extraction based or commercial chitosan supplements. The pH, temperature, ammonia nitrogen, blood urea and microbial count were similar among treatments. The different sources of chitosan supplements did not change the totals of volatile fatty acids, acetate and butyrate; in contrast, different chitosan sources influenced (P<0.05) propionate content. The ruminal acetate to propionate ratio was markedly (P<0.05) reduced with chitosan supplement, but no change appeared between sources of chitosan. At 4 hours after feeding, the methane estimation signiﬁcantly decreased with the addition of chitosan supplementation (P<0.05) compared to the control group. The purine derivatives and microbial protein synthesis were not altered by the treatments. No significant differences existed on milk yield, milk composition or milk urea nitrogen when cows received different sources of chitosan (P>0.05). In sum, supplementing extracted chitosan showed more potential than did commercial chitosan for enhancing economic efficiency and recycling shrimp residues, therefore, reducing environmental waste.
ARTICLE | doi:10.20944/preprints202010.0031.v1
Subject: Chemistry, Analytical Chemistry Keywords: primary fatty acid amides; microfluidics; laser induced fluorescence, bioactive lipids
Online: 2 October 2020 (09:16:13 CEST)
The inherent trace quantity of primary fatty acid amides found in biological systems presents challenges for analytical analysis and quantitation, requiring a highly sensitive detection system. The use of microfluidics provides a green sample preparation and analysis technique through small-volume fluidic flow through micron-sized channels embedded in a PDMS device. Microfluidics provides the potential of having a micro total analysis system where chromatographic separation, fluorescent tagging reactions, and detection are accomplished with no added sample handling. This study describes the development and optimization of a microfluidic-laser indued fluorescence (LIF) analysis and detection system that can be used for the detection of ultra-trace levels of fluorescently tagged primary fatty acid amines. A PDMS microfluidic device was designed and fabricated to incorporate droplet-based flow. Droplet microfluidics have enabled on-chip fluorescent tagging reactions to be performed quickly and efficiently, with no additional sample handling. An optimized LIF optical detection system provided fluorescently tagged primary fatty acid amine detection sub-fmol (436 amol) LODs. The use of this LIF detection provides unparalleled sensitivity, with detection limits several orders of magnitude lower than currently employed LC-MS techniques and might be easily adapted for use as a complementary quantification platform for parallel MS-based -omics studies.
ARTICLE | doi:10.20944/preprints202009.0484.v1
Subject: Biology, Physiology Keywords: lipoprotein lipase; neuronal metabolism; fatty liver; brain-liver-axis; FLIM
Online: 20 September 2020 (15:32:43 CEST)
The autonomic regulation of hepatic metabolism offers a novel target for the treatment of non-alcoholic fatty liver disease (NAFLD). However, the molecular characteristics of neurons that regulate the brain-liver axis remain unclear. Since mice lacking neuronal lipoprotein lipase (LPL) develop perturbations in neuronal lipid-sensing and systemic energy balance, we reasoned that LPL might be a component of pre-autonomic neurons involved in the regulation of hepatic metabolism. Here we show that despite obesity, mice with reduced neuronal LPL (NEXCreLPLflox [LPL KD]) show improved glucose tolerance and reduced hepatic lipid accumulation with aging compared to WT controls (LPLflox). To determine the effect of LPL deficiency on neuronal physiology, liver-related neurons were identified in the paraventricular nucleus (PVN) of the hypothalamus using the transsynaptic retrograde tracer PRV-152. Patch-clamp studies revealed reduced inhibitory post-synaptic currents in liver-related neurons of LPL KD mice. Fluorescence Lifetime Imaging Microscopy (FLIM) was used to visualize metabolic changes in LPL-depleted neurons. Quantification of the free vs. bound Nicotinamide Adenine Dinucleotide (NADH) and Flavin Adenine Dinucleotide (FAD) revealed increased glucose utilization and TCA cycle flux in LPL-depleted neurons compared to controls. Global metabolomics from hypothalamic cell lines either deficient in, or over-expressing, LPL recapitulated these findings. Our data suggest that LPL is a novel feature of liver–related preautonomic neurons in the PVN. Moreover, LPL loss is sufficient to cause changes in neuronal substrate utilization and function, which may precede changes in hepatic metabolism.
REVIEW | doi:10.20944/preprints202008.0174.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: diet; plant sterols; stanols; omega-3 fatty acids; familial hypercholesterolemia
Online: 7 August 2020 (06:13:47 CEST)
Background: Although a cholesterol-lowering diet and the addition of plant sterols and stanols are suggested for the lipid management of children and adults with familial hypercholesterolemia, there is limited evidence evaluating such interventions in this population. Objectives: To investigate the impact of cholesterol-lowering diet and other dietary interventions on the incidence or mortality of cardiovascular disease and lipid profile of patients with familial hypercholesterolemia. Search methods: Relevant trials were identified by searching US National Library of Medicine National Institutes of Health Metabolism Trials Register and clinicaltrials.gov.gr using the following terms: diet, dietary, plant sterols, stanols, omega-3 fatty acids, fiber and familial hypercholesterolemia. Selection criteria: Randomized controlled trials evaluating the effect of cholesterol-lowering diet or other dietary interventions in children and adults with familial hypercholesterolemia were included. Data collection and analysis: Two authors independently assessed the trial eligibility and bias risk and one extracted the data, with independent verification of data extraction by a colleague. Results: A total of 17 trials were finally included, with a total of 376 participants across 8 comparison groups. The included trials had either a low or unclear bias risk for most of the parameters used for risk assessment. Cardiovascular incidence or mortality were not evaluated in any of the included trials. Among the planned comparisons regarding patients’ lipidemic profile, a significant difference was noticed for the following comparisons and outcomes: omega-3 fatty acids reduced triglycerides (mean difference [MD]: -0.27 mmol/L, 95% confidence interval [CI]: -0.47 to -0.07, p<0.01) when compared with placebo. A non-significant trend towards a reduction in subjects’ total cholesterol (MD: -0.34, 95% CI: -0.68 to 0, mmol/L, p=0.05) and low-density lipoprotein cholesterol (MD: -0.31, 95% CI: -0.61 to 0, mmol/L, p=0.05) was noticed. In comparison with cholesterol-lowering diet, the additional consumption of plant stanols decreased total cholesterol (MD: -0.62 mmol/l, 95% CI: -1.13 to -0.11, p=0.02) and low-density lipoprotein cholesterol (MD: -0.58 mmol/l, 95% CI: -1.08 to -0.09, p=0.02). The same was by plant sterols (MD: -0.46 mmol/l, 95% CI: -0.76 to -0.17, p<0.01 for cholesterol, and MD: -0.45 mmol/l, 95% CI: -0.74 to -0.16, p<0.01 for low-density lipoprotein cholesterol). No heterogeneity was noticed among the studies included in these analyses. Conclusions: Available trials confirm that the addition of plant sterols or stanols has a cholesterol-lowering effect on such individuals. On the other hand, supplementation with omega-3 fatty acids effectively reduces triglycerides and might have a role in lowering the cholesterol of patients with familial hypercholesterolemia. Additional studies are needed to investigate the effectiveness of a cholesterol-lowering diet or the addition of soya protein and dietary fibers to a cholesterol-lowering diet in familial hypercholesterolemia.
ARTICLE | doi:10.20944/preprints201912.0250.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: fatty infiltration; main pancreatic duct dilatation; pancreatic invasive ductal adenocaricinoma
Online: 19 December 2019 (07:19:10 CET)
Background: Pancreatic invasive ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality in Japan. The early diagnosis of pancreatic cancer, which will increase the number of patients with resectable tumors, is urgently needed. The purpose of the present study was to examine the earliest signs of pancreatic abnormalities on CT in order to facilitate the diagnosis and treatment of PDAC. Methods: Forty-one patients with pancreatic cancer and their 154 CTs were selected for the present study. We used the images that were acquired prior to the diagnosis and examined the pancreas in these images to observe serial changes in the morphology of the pancreas after selecting CT images in which PDAC was suspected. We also confirmed whether the main pancreatic duct was observed around that area of the pancreas. Four thousand two hundred seventy-seven patients without pancreato-biliary disease with 4630 CTs were selected for the control group. Results: Two pancreas shapes were detected: localized constriction of the pancreatic parenchyma referred to as the K-shaped sign, and localized fatty changes. Twenty-four (58.5%) of 41 patients showed the K-shaped sign. The main pancreatic duct without dilatation was noted around the K-shaped sign in 9 of the 24 patients. Eight of 41 patients (19.5%) showed localized fatty changes. Nine of 41 patients (21.9%) showed no abnormality. In the control group, only seven of 4277 patients (0.16%) showed the K-shaped sign. Conclusions: The K-shaped sign including localized fatty changes is the earliest CT sign that presents with pancreatic abnormalities. The K-shaped sign does not indicate PDAC itself but may predict its future development.
Subject: Medicine & Pharmacology, Allergology Keywords: sarcopenia; non-alcoholic fatty liver disease; obesity; skeletal muscle mass; inflammation
Online: 14 December 2020 (08:20:04 CET)
Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated bidirectional relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass <0.789 in men and <0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs=1.213, 95% CIs=1.050–1.402). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs=1.564, 95% CIs=1.378–1.775). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a bidirectional relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.
ARTICLE | doi:10.20944/preprints202004.0109.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: insulin-resistance; hyperlipidemia; non alcoholic fatty liver disease (NAFLD); OCTN1; OCTN2
Online: 8 April 2020 (03:22:50 CEST)
Hyperlipidemia and insulin-resistance are often associated with Non Alcoholic Fatty Liver Disease (NAFLD) thereby representing a true issue worldwide, due to increased risk of developing cardiovascular and systemic disorders. Although clear evidence suggests that circulating fatty acids contribute in pathophysiological mechanisms underlying NAFLD and hyperlipidemia, further studies are required for better identify potential beneficial approaches for counteracting such a disease state. Recently, several artichoke extracts have been used for both reducing hyperlipidemia, insulin-resistance and NAFLD, though the mechanism is unclear. Here we used a wild type of Cynara Cardunculus extract (CyC), rich in sesquiterpens and antioxidant active ingredients, in rats fed and High Fat Diet (HFD) compared to Normal Fat Diet (NFD). In particular, in rats fed HFD for four consecutive weeks, we found a significant increase of serum cholesterol, triglyceride and serum glucose. This effect was accompanied by increased body weight and by histopathological features of liver steatosis. The alterations of metabolic parameters found in HFD were antagonised dose-dependently by daily oral supplementation of rats with CyC 10 and 20 mg/Kg over 4 weeks, an effect associated to significant improvement of liver steatosis. The effect of CyC (20 mg/Kg) was also associated to enhanced expression of both OCTN1 and OCTN2 carnitine-linked transporters. Thus, present data suggest a contribution of carnitine system in the protective effect of CyC in diet-induced hyperlipidemia, insulin-resistance and NAFLD.
ARTICLE | doi:10.20944/preprints201908.0069.v1
Subject: Medicine & Pharmacology, Other Keywords: coenzyme Q deficiency; mitochondrial disease; respiratory chain; fatty acids; myopathy; ADCK2
Online: 6 August 2019 (07:52:35 CEST)
Fatty acids and glucose are the main bioenergetic substrates in mammals that are alternatively used during the transition between fasting and feeding. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data show that Aldh2+/- mice exhibits impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in CoQ biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.
REVIEW | doi:10.20944/preprints201907.0289.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: omega-3 polyunsaturated fatty acids; Parkinson’s disease; Alzheimer’s disease; clinical trials
Online: 25 July 2019 (11:38:57 CEST)
A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of antinflammatory mediators, cell membrane fluidity, intracellular signalling and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represent a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.
ARTICLE | doi:10.20944/preprints201902.0001.v2
Subject: Chemistry, Analytical Chemistry Keywords: color; free fatty acids; iodine absorption value; paraanisidine value; peroxide value
Online: 6 February 2019 (06:36:41 CET)
Deep fat frying is not novel, but a classical antiquity culinary technique preferred chiefly for its swiftness, amenity, conferment of a crisp texture, attractive sensorial and organoleptic qualities and thus delectableness of the fries. Regrettably, repeated use of oils for deep frying impacts the storage life and nutritional suitability of fries. This concerted study investigated the effects of continuous deep fat frying on the physicochemical properties of ten brands of edible cooking oils: Fortune Butto, Roki, Tamu, Best Fry, Golden Fry, Mukwano, Sunny, Sunvita, Sunlite and Sunseed used in deep frying of potato chips in Kampala, Uganda. Three oil samples from local Irish chip fryers were also collected. The color value (CV) and the acidification of the oils as free fatty acid (FFA), peroxide value (POV), paraanisidine value (AnV) and iodine adsorption value (IV) before and between ten successive deep-fryings using potato chips were determined. The possible reuse of the oils was estimated from the frying round when a quality criterion surpassed national or CODEX specifications for the respective edible cooking oils. For fresh oils, the statistical parameter ranges were: CV (0.4R 3.4Y-7.7R 70Y), % FFA (0.0430-0.1508), POV (0.5951-6.6134 meqO2/Kg), AnV (0.90-4.30) and IV (57.62-128.35gI2/100g). By the tenth fry, the values were respectively 3.0R 23Y-20.4R 70Y, 0.2286-0.4817, 11.1138-15.7525 meqO2/Kg, 10.31-22.16 and 53.66-126.03 gI2/100g. Reuse of the oils for continuous frying of potatoes on the same day can be done only up to 7 times on average for hard oils and 6 times for soft oils.
ARTICLE | doi:10.20944/preprints201810.0712.v1
Subject: Biology, Animal Sciences & Zoology Keywords: diacylglycerol acyl-CoA acyltransferase (DGAT1); K232A; milk traits; milk fatty acid
Online: 30 October 2018 (08:46:38 CET)
Milk fat production is important in the New Zealand (NZ) dairy industry. Elsewhere, an amino acid substitution (K232A) in the enzyme diacylglycerol acyl-CoA acyltransferase (DGAT1) has been reported to explain variation in some milk traits, including variation in milk fatty acid (FA) profile. In this study, associations between K232A, and milk traits including milk FA composition, were studied in wholly pasture-fed NZ Holstein-Friesian × Jersey (HF×J) cross-bred dairy cows. With a high frequency of K variant (61.9%), the KK cows produced more milk fat than the AA cows (5.41 ± 0.04 % vs 4.42 ± 0.05 %). The milk volume, fat concentration and protein concentration of AK cows were between the genotypes, AA and KK. More C16:0, CLA and C18:3 cis-9, 12, 15 FA were found in the milk of Kiwi-cross cows feed in outdoor pasture grazing system., and the influence of DGAT1 K232A, on these FAs from mid- and late lactation stages were significant. The AA cows produced (P < 0.001) more CLA and C18:3 cis-9, 12, 15, but less C16:0 (1.137 ± 0.047, 0.855 ± 0.015 and 35.170 ± 0.355) than the KK cows (0.934 ± 0.025, 0.778 ± 0.009 and 38.010 ± 0.250).
ARTICLE | doi:10.20944/preprints201810.0449.v1
Subject: Life Sciences, Biotechnology Keywords: green algae; biomass; fatty acids; Tetraselmis straiata; lipids; carotenoids; raceway ponds
Online: 19 October 2018 (11:09:56 CEST)
In the process of modernization and development, a human being always needed energy, which increased the dependency on the available sources of fossil fuel. Tetraselmis, a green algal genus belong to the order Chlorodendrales, are described by their strong green coloured chloroplast, flagellated cell bodies, and the occurrence of a pyrenoid within the chloroplast. In this study, four different strains of Tetraselmis species were successfully isolated from the saltpans Kovelong, Chennai, Tamil Nadu, India. The isolated strains were cultured in the normal basal medium and their morphological features were subsequently studied. The species of Tetraselmis straiata (T. straiata) Butcher BBRR1 was confirmed using molecular identification of 18S rRNA gene analysis and its observed systematic position. Among the four different isolates, T. straiata Butcher BBRR1 recorded a highest biomass concentration of 0.58 ± 0.021 g L-1, 15% lipids, 19% proteins and 17% carbohydrates when it grown under laboratory condition. Whereas, in open raceway ponds, T. straiata BBRR1 produced 0.95 ± 0.06 g L-1 biomass, 19% lipids, 28% proteins and 21% carbohydrates in an modified CFTRI I medium. The fatty acids profile of T. straiata Butcher BBRR1showed the presence of 33.14 % Palmitic acid, 22.64% 11- Octadecenoic acid and 21.94% Heptadecanoic acid. Since T. straiata BBRR1 can be cultivated in open ponds without a major contaminations, this species can be used as novel biomass feedstock to produce biofuels. This study may suggest the potential of T. straiata BBRR1 for biofuel production and could compete the energy demand in the future. In addition, this species contains healthful components of carotenoids, lipids and proteins, all these may provide a health benefits beyond basic nutrition.
ARTICLE | doi:10.20944/preprints201707.0026.v2
Subject: Life Sciences, Microbiology Keywords: agavins; prebiotics; microbiota; overweight; body weight loss; short chain fatty acids
Online: 25 July 2017 (04:52:34 CEST)
Agavins consumption has lead to accelerate body weight loss in mice. We investigated the changes on cecal microbiota and short chain fatty acids (SCFA) associated to body weight loss in overweight mice. Firstly, mice were fed with standard (ST5) or high fat (HF5) diet for 5 weeks. Secondly, overweight mice were shifted to standard diet alone (HF-ST10) or supplemented with agavins (HF-ST+A10) or oligofructose (HF-ST+O10), five more weeks. Cecal contents were collected before and after supplementation to determine microbiota and SCFA concentrations. At the end of first phase, HF5 mice showed a significant increase of body weight, which was associated with reduction of cecal microbiota diversity (PD whole tree; non-parametric t-test, P < 0.05), increased Firmicutes/Bacteroidetes ratio and reduced SCFA concentrations (t-test, P < 0.05). After diet shifted, HF-ST10 normalized its microbiota, increase its diversity and SCFA levels, whereas agavins (HF-ST+A10) or oligofructose (HF-ST+O10) led to partial microbiota restoration, with normalization of the Firmicutes/Bacteroides ratio as well as higher SCFA levels (P < 0.1). Moreover, agavins noticeably enriched Klebsiella and Citrobacter (LDA > 3.0); this enrichment has not been reported previously under a prebiotic treatment. In conclusion, agavins or oligofructose modulated cecal microbiota composition, reduced extent of diversity and increased SCFA. Furthermore, identification of bacteria enriched by agavins, opens opportunities to explore new probiotics.
ARTICLE | doi:10.20944/preprints202207.0063.v1
Subject: Biology, Animal Sciences & Zoology Keywords: Native shrubs; In vitro fermentation; volatile fatty acids; greenhouse gases; hill country
Online: 5 July 2022 (07:40:50 CEST)
Information on the nutritive value and in vitro fermentation characteristics of native shrubs in New Zealand is scant. This is despite their potential as alternatives to exotic trees and shrubs for sup-plementary fodder, and mitigation of greenhouse gas and soil erosion on hill country sheep and beef farms. The objectives of this study were to measure the in vitro fermentation gas production, predict parameters of in vitro fermentation kinetics and to estimate in vitro fermentation of volatile fatty acids (VFA), microbial biomass (MBM) and greenhouse gases of four native shrubs (Coprosma robusta, Griselinia littoralis, Hoheria populnea and Pittosporum crassifolium) and an exotic fodder tree species, Salix schwerinii. Total in vitro gas production was higher (p<0.05) for natives than S. schwerinii. Prediction using the single pool model resulted in biologically incorrect negative in vitro total gas production from the immediately soluble fraction of the native shrubs. However, the dual pool model better predicted in vitro total gas production and was in alignment with measured in vitro fermentation end products. In vitro VFA and greenhouse gas production from fermentation of leaf and stem material were higher (p<0.05), and MBM lower (p<0.05), for native shrubs com-pared to S. schwerinii. The lower in vitro total gas production, VFA and greenhouse gases produc-tion, and higher MBM of S. schwerinii may be explained by the presence of condensed tannins (CT), although this was not measured and requires further study. In conclusion, results from this study suggests that when consumed by ruminant livestock, the browsable native shrubs can provide adequate energy and microbial protein, and that greenhouse gas production from these species is within ranges reported for typical New Zealand pastures.
ARTICLE | doi:10.20944/preprints202204.0236.v1
Subject: Life Sciences, Biochemistry Keywords: biorefining; by-products; enzymatic hydrolysis; essential fatty acids; green-extraction; lipids; sustainability
Online: 26 April 2022 (10:37:03 CEST)
The main intention of the present work was to investigate the ability of cellulose-degrading enzymes (C-DE) to release fatty acids (FAs) from complex matrices of cereal by-products during enzymatic hydrolysis (EH). For this purpose, three types of cereal bran (CB), i.e., wheat, rye, and oat were used as a lignocellulose substrate for three commercially available hydrolytic enzymes, i.e., Viscozyme L, Viscoferm, and Celluclast 1.5 L. The yield and composition of FAs after EH was assessed and confronted with the yield obtained after either conventional Soxhlet extraction or alkaline-assisted hydrolysis (A-AH) with 10% KOH in 80% MeOH and subsequent liquid-liquid extraction. The experimental results demonstrated that up to 6.3% and 43.7% higher total FAs yield can be achieved within EH of rye bran using Celluclast 1.5 L than by A-AH and Soxhlet extraction, respectively. However, the application of Viscoferm for EH of wheat bran ensured up to 7.7% and 13.4% higher total FAs yield than A-AH and Soxhlet extraction, respectively. The concentration of essential linolenic acid (C18:3) in lipids extracted after EH of rye bran with Celluclast 1.5 L was up to 24.4% and 57.0% higher than in lipids recovered by A-AH and Soxhlet extraction, respectively. In turn, the highest content of linolenic in wheat bran lipids was observed after EH with Viscoferm and Viscozyme L, ensuring 17.0 and 13.6% higher yield than after A-AH, respectively. SEM analysis confirmed substantial degradation of CB matrix promoted by the ability of C-DE to act specifically on 1,4-β-D-glycosidic bonds in cellulose and on 1,2-α-,1,3-α-, and 1,5-α-L- arabinofuranoside and 1,4-β-D-xylosidic bonds in arabinoxylans, arabinans, and other arabinose-containing hemicelluloses. Structural alteration in cells integrity greatly contributed to the release of bound FAs and their better transfer into the extraction solvent. It has been shown that the proposed process of EH can be used for the efficient release of FAs from the CB matrix more sustainably and with a safer profile, thereby representing the further sustainable production of FAs for certain purposes.
REVIEW | doi:10.20944/preprints202103.0712.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: dietary fibers; short chain fatty acid; gut microbiota; colorectal cancer prevention; epigenetics
Online: 29 March 2021 (22:22:00 CEST)
Dietary factors play an important role in shaping the gut microbiome which, in turn, regulates the molecular events in colonic mucosa. The composition and resulting metabolism of the gut microbiome have been implicated in the development of colorectal cancer (CRC). Diets low in dietary fibers and phytomolecules as well as other lifestyle-related factors may predispose to CRC. Emerging evidence demonstrates that the predominance of microbes, such as Fusobacterium nucleatum, can predispose the colonic mucosa to malignant transformation. Dietary and lifestyle modifications have been demonstrated to restrict the growth of potentially harmful opportunistic organisms. In this study, we aim to present evidence regarding the relationship of dietary factors to the gut microbiome and development of CRC.
REVIEW | doi:10.20944/preprints202012.0822.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Sarcopenia; Non-alcoholic Fatty Liver Disease; Obesity, Insulin Resistance; Prevalence; Metabolic Diseases
Online: 31 December 2020 (15:34:29 CET)
Non-alcoholic fatty liver disease (NAFLD) continues to rise and has become the most common cause of chronic liver disease among all ages and ethnicities. Metabolic disorders such as obesity and insulin resistance are closely associated with sarcopenia and NAFLD. Sarcopenic obesity is a clinical disorder characterized by the simultaneous loss of skeletal muscle and gain of adipose tissue. It is associated with worse outcomes in individuals with NAFLD. It is projected that NAFLD and sarcopenia will rise as the prevalence of obesity continues to increase at an unparallel rate. Recently, sarcopenia and sarcopenic obesity have gained considerable interest, but we still lack a well-defined definition and a management approach. Therefore, it is imperative to continue shining the light on this topic and better understand the underlying mechanism as well as treatment options. In this review article, we aimed to address the pathophysiology, impact, and outcomes of sarcopenic obesity on NAFLD.
ARTICLE | doi:10.20944/preprints202010.0563.v1
Subject: Life Sciences, Biochemistry Keywords: diabetes; omega-3 polyunsaturated fatty acid; lipoprotein subfraction; dyslipidemia; randomized controlled trial
Online: 27 October 2020 (20:37:15 CET)
Objectives To determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) from animal and plant sources on glucolipid metabolism and lipoprotein subfractions in type 2 diabetic patients with dyslipidemia. Methods Participants were recruited from the diabetes clinic at the Guanlin Hospital, Yixing City in Jiangsu province, China, from March 2017 through June 2017. Ninety participants were randomly assigned to take 3g/day fish oil (FO, containing EPA and DHA), 3g/day perilla oil (PO, containing ALA), or 3g/day blend oil containing fish oil and linseed oil (BO, containing EPA, DHA and ALA) for 3 months. The levels of serum glucose, glycated hemoglobin (HbA1c), C-peptide, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), lipoprotein a (Lp(a)), and free fatty acids were determined at baseline and after the 3 months. In addition, four fatty acids in serum and red blood cells membranes (RBCm) were analyzed using gas chromatography-mass spectrometry. The Lipoprint System was used to determine the lipoprotein subfractions. Results All 90 participants completed the final 3-month follow-up at the end of the study. After three months of intervention, blood glucose and HbA1c levels in the PO group were significantly lower than those at the baseline (p < 0.05). On the other hand, in the BO group, the HbA1c, non-HDL, Apo A1 and Lp(a) levels were significantly lower, while the C-peptide levels were significantly higher after intervention compared to the baseline (p < 0.05). In the FO group, the HbA1c and TG levels were significantly lower after the intervention compared to the baseline (p < 0.05). In addition, at the end of the study, there was significant increase in the levels of DPA and DHA in serum and RBCm of the FO group (p < 0.05), while in the BO group, there was significant increase in the levels of EPA, DPA and DHA in RBCm (p < 0.05). Finally, the FO group had the highest levels of large HDL subfractions compared to the BO and PO groups, but had the lowest levels of small HDL subfractions among the three groups. Conclusion For patients with diabetes, plant-derived ω-3 PUFAs are more effective at controlling blood glucose than animal-derived ω-3 PUFAs. However, animal-derived ω-3 PUFAs play a critical role in controlling blood lipids. Particularly, fish oil can effectively increase the beneficial large HDL subfractions and reduce the nonbeneficial small HDL subfractions. Both the animal- and plant-derived ω - 3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.
ARTICLE | doi:10.20944/preprints202010.0133.v1
Subject: Biology, Anatomy & Morphology Keywords: Biomarkers; Fatty acid profile; Halogenated compounds; Oxidative stress; Red macroalgae; Secondary metabolites
Online: 6 October 2020 (14:52:20 CEST)
The red seaweed Asparagopsis armata exhibits a strong invasive behaviour and is included in the list of the “Worst invasive alien species threatening biodiversity in Europe”. This seaweed has been shown to produce a large diversity of halogenated compounds with effective biological effects, deeply affecting rockpool species. Therefore, the present study aimed to investigate the biochemical responses to sublethal concentrations of Asparagopsis armata exudate on two coastal organisms, the marine snail Gibbula umbilicalis and the rockpool shrimp Palaemon elegans. Antioxidant defences superoxide dismutase (SOD) and glutathione-S-transferase (GST), oxidative damage endpoints lipid peroxidation (LPO) and DNA damage, the neuronal parameter acetylcholinesterase (AChE), as well as the fatty acid profile were evaluated. Results revealed different metabolic responses between species, indicating that A. armata exudate affected the organisms through different pathways. Despite previous studies indicating that the exudate effected G. umbilicalis’ survival and behaviour, this does not seem to result from oxidative stress or addressed neurotoxicity. On the other hand, for P. elegans, an inhibition of AChE and the decrease of antioxidant capacity concomitant with the increase of LPO, suggests neurotoxicity and oxidative stress as mechanisms of exudate toxicity for this species. For fatty acids, there were different profile changes between species, also more pronounced for P. elegans with a general increase in PUFA with exudate exposure, which commonly means a defence mechanism protecting from membrane disruption. Nonetheless, the omega-3 PUFAs ARA and DPA were increased in both invertebrates, indicating a common mechanism regulation of inflammation and immunity responses to this stress. This work provides further insight on the mechanisms of invertebrate response and tolerance to an expanding coastal environmental stress as is the marine invader A. armata.
ARTICLE | doi:10.20944/preprints202005.0127.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; liver fibrosis; amino acids; insulin resistance
Online: 7 May 2020 (13:29:39 CEST)
Altered amino acid levels have been found in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). However, it is not clear whether this alteration is due to altered hepatic metabolism or insulin resistance. The aim of this study was to clarify the association among amino acid levels, fatty liver, and liver fibrosis while eliminating the influence of insulin resistance. NAFLD and liver fibrosis were diagnosed using transient elastography and subjects were divided in three groups: normal, NAFLD, and liver fibrosis. To exclude the influence of insulin resistance, the subjects were matched using the homeostasis model assessment of insulin resistance (HOMA-IR). The amino acid serum levels were compared among the groups. Of 731 enrolled subjects, 251 and 33 were diagnosed with NAFLD and liver fibrosis. Although significant differences were observed among the groups in the serum levels of most amino acids, all but those of glutamate and glycine disappeared after matching for HOMA-IR. The multivariate logistic regression revealed that glutamate, glycine, and HOMA-IR were independent risk factors for liver fibrosis. The altered serum levels of most amino acids were associated with insulin resistance, while the increase in glutamate and the decrease in glycine levels were strongly associated not only with insulin resistance, but also with altered liver metabolism in patients with liver fibrosis.
ARTICLE | doi:10.20944/preprints201809.0169.v1
Subject: Biology, Animal Sciences & Zoology Keywords: European sardine; draft genome; teleosts; comparative genomics; long chain polyunsaturated fatty acids
Online: 10 September 2018 (12:37:23 CEST)
Clupeiformes, such as sardines and herrings, represent an important share of worldwide fisheries. Among those, the European sardine (Sardina pilchardus, Walbaum 1792) exhibits significant commercial relevance. While the last decade showed a steady and sharp decline in capture levels, recent advances in culture husbandry represent promising research avenues. Yet, the complete absence of genomic resources from sardine imposes a severe bottleneck to understand its physiological and ecological requirements. We generated 69 Gbp of paired-end reads using Illumina HiSeq X Ten and assembled a draft genome assembly with an N50 scaffold length of 25579 bp and BUSCO completeness of 82.1% (Actinopterygii). The estimated size of the genome ranges between 655 and 850 Mb. Additionally, we generated a relatively high-level liver transcriptome. To deliver a proof of principle of the value of this dataset, we established the presence and function of enzymes (elovl2, elovl5 and fads2) that have pivotal roles in the biosynthesis of long chain polyunsaturated fatty acids, essential nutrients particularly abundant in oily fish such as sardines. Our study provides the first omics dataset from a valuable economic marine teleost species, the European sardine, an essential resource for their effective conservation, management and sustainable exploitation.
ARTICLE | doi:10.20944/preprints201701.0117.v1
Subject: Life Sciences, Molecular Biology Keywords: blunt snout bream; high carbohydrate; transcriptome; metabolomics; insulin resistance; fatty liver disease
Online: 26 January 2017 (03:52:10 CET)
A high intake of carbohydrates, associated with obesity, is one of the major causes of fatty liver disease in humans. This study investigated how high carbohydrate intake induces fatty liver disease in Blunt snout bream (Megalobrama amblycephala). Blunt snout bream were fed a high-carbohydrate diet (HCBD) for 60 days. Their growth indices were evaluated, and the transcriptomes, metabolites, biochemistry, and histology of their blood and livers were analyzed. The final weight, weight gain, specific growth rate, and feed conversion ratio were all higher in the HCBD group than in the control group, but not significantly so (P > 0.05). The hepatosomatic index (HSI) differed significantly in the two groups (P < 0.05), and the metabolomics results showed that a high carbohydrate intake induced significant increases in plasma α/β-glucose, succinate, and tyrosine, which could increase hepatic glycogen and triglyceride. Low levels of betaine were also found in the livers of the HCBD group. The histology and blood biochemistry results suggested abnormal liver, with excessive lipid accumulation and liver damage. A transcriptome analysis and quantitative reverse transcription–PCR (RT–qPCR) indicated that the expression of the factors INSR, IRS, PI3K, PDK, AKT, ACC, IL6, AP1, ChREBP-MLX, PEPCK, and FBP in the insulin signaling pathway was significantly upregulated and that of SOCS3, GSK3β, and AMPK significantly downregulated in the HCBD. This pattern is associated with the nonalcoholic fatty liver disease (NAFLD) pathway. This study extends our understanding of how high carbohydrate causes increased fat deposition in the liver, enhanced glycolysis (α/β-glucose) in the plasma, and reduced betaine in the liver. This leads to activation of hepatocyte insulin resistance and lipogenesis by regulating the expression of genes related to fatty liver disease.
REVIEW | doi:10.20944/preprints202209.0320.v1
Subject: Chemistry, Organic Chemistry Keywords: marine natural products; oxygen heterocycles; tetrahydrofuran; total synthesis; biological activity; terpenes; fatty acids.
Online: 21 September 2022 (10:04:09 CEST)
heterocycles are particularly common moieties within marine natural products. Specifically, tetrahydrofuranyl rings are present in a variety of compounds which present complex structures and interesting biological activities. Focusing on terpenoids, a high number of tetrahydrofuran-containing metabolites have been isolated during the last decades. They show promising biological activities, making them potential leads for novel antibiotics, antikinetoplastid drugs, amoebicidal substances or anticancer drugs. Thus, they have attracted the attention of the synthetic community, and numerous approaches to their total syntheses have appeared. Here, we offer the reader an overview of marine-derived terpenoids and related compounds, with a special focus on their isolation, structure determination, biological profiles and total syntheses.
COMMUNICATION | doi:10.20944/preprints202105.0090.v1
Subject: Biology, Anatomy & Morphology Keywords: Orphan crops; polyunsaturated fatty acids; α-linolenic acid; food security; traditional crops; oilseeds
Online: 6 May 2021 (14:53:18 CEST)
Plukenetia volubilis is an underutilized oilseed crop native to the Amazon basin, where it has been utilised by humans since Incan times. The large seeds contain approx. 45–50 % lipid, of which approx. 35.2–50.8 % is α-linolenic acid (C18:3 n-3, ω-3) and approx. 33.4–41.0 % is linoleic acid (C18:2 n-6, ω-6), the two essential fatty acids required by humans. The seeds also contain 22–30 % protein and have antioxidant properties. Due to its excellent nutritional composition and good agronomic properties, it has attracted increasing attention in recent years, and cultivation is expanding. When considering current global challenges, a reformation of our food systems is imperative in order to ensure food security, mitigation of climate change, and alleviation of malnutrition. For this purpose, underutilized crops may be essential tools, which can provide agricultural hardiness and reduced need for external inputs, climate resilience, diet diversification, and improved income opportunities for smallholders. Plukenetia volubilis is a promising up and coming crop in this regard and has considerable potential for further domestication; it has an exceptional oil composition, good sensory acceptability, is well suited for cultivation, and has numerous potential applications in, e.g. gastronomy, medicine, and cosmetics.
ARTICLE | doi:10.20944/preprints201907.0247.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: opioid; microbiome-brain axis; DHA; anxiety; polyunsaturated fatty acids; intravenous self-administration; mice
Online: 23 July 2019 (04:09:40 CEST)
Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 fatty acids such as docosahexaenoic acid (DHA), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that a diet enriched in polyunsaturated fat acids (PUFAs) ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and DHA supplementation. We demonstrate that withdrawal of opioids led to a significant depletion in specific microbiota genera whereas DHA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that DHA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction.
ARTICLE | doi:10.20944/preprints201901.0041.v1
Subject: Biology, Physiology Keywords: nonalcoholic fatty liver disease; high fat-sucrose diet; metabolomics; HPLC-QTOF-MS; quercetin
Online: 4 January 2019 (14:04:13 CET)
As metabolomics is widely used in the study of disease mechanisms, more and more studies have found that metabolites play an important role in the occurrence of diseases. The aim of this study is to investigate the effects and mechanisms of quercetin in high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) development using nontargeted metabolomics. A rat model of NAFLD was established by feeding with a HFD for 30 and 50 days. Results indicated quercetin exhibited hepatoprotective activity in HFD-induced NAFLD rats in 30 days by regulating fatty acids related metabolites (adrenic acid, etc.), inflammation related metabolites (arachidonic acid, etc.), oxidative stress related metabolites (2-hydroxybutyric acid) and other differential metabolites (citric acid, etc.). However, quercetin couldn’t improve NAFLD in 50 days maybe it couldn’t reverse the inflammation condition induced by long-term high-fat diet. These data indicate that dietary quercetin may be beneficial to NAFLD at early stages. Furthermore, combining metabolomics and experimental approaches opens up avenues of effects and mechanisms of drugs for complex diseases.
ARTICLE | doi:10.20944/preprints201709.0039.v1
Subject: Chemistry, Food Chemistry Keywords: stable carbon isotope analysis; lipids; fatty acids; Cordyceps sinensis; the Qinghai-Tibetan Plateau
Online: 11 September 2017 (08:06:30 CEST)
Cordyceps sinensis is one rare medicinal fungus produced in the Qinghai-Tibetan Plateau. Its quality and price varies hugely with different habitat, and its numerous substitutes have sprung up in functional food markets. This paper aims to discriminate the geographic origin of wild C. sinensis and its substitutes via the element analyzer-isotope ratio mass spectrometry and gas chromatography-isotope ratio mass spectrometry. The δ13C values of major fatty acids in the lipids of Cordyceps sinensis are characterized unanimously by the variation relation C18:0 ﹤ C18:2 ≈ C16:0 ﹤ C18:1; while their fluctuation intervals are notably different between those of neutral and polar lipids. The comparative analysis of the δ13C ratios of major fatty acids in lipids of Cordyceps sinensis suggests that the δ13C patterns may be sensitive potential indicators to discriminate its geographical origin. The δ13C values of individual major fatty acids of lipids from the cultivated stromata of Cordyceps militaris (SCM), the fermented mycelia of Hirsurella sinensis (FMH) and Paecilomyces epiali (FMP) range from −31.2‰ to −29.7‰, −16.9‰ to −14.3‰, and −26.5‰ to −23.9‰, respectively. Their δ13C pattern of individual major fatty acids may be used as a potential indicator to discriminate the products of natural C. sinensis and its substitutes.
CASE REPORT | doi:10.20944/preprints201704.0051.v1
Subject: Medicine & Pharmacology, Other Keywords: carnitine palmitoyltransferase deficiency; CPT1A; fatty acid oxidation disorders; transaminitis; Ashkenazi Jewish; neonatal screening
Online: 10 April 2017 (06:23:32 CEST)
An 18 month-old male was evaluated after presenting with disproportionate transaminitis in the setting of acute gastroenteritis. He had marked hepatomegaly on physical exam that was later confirmed with an abdominal ultrasound. Given this clinical picture, suspicion for a fatty acid oxidation disorder was raised. Further investigation revealed that his initial newborn screen was positive for carnitine palmitoyltransferase 1A (CPT1A) deficiency - a rare autosomal recessive disorder of long-chain fatty acid oxidation. Confirmatory biochemical testing in the newborn period showed carnitine levels to be unexpectedly low with a normal acylcarnitine profile. Thus, it was considered to be a false-positive newborn screen and metabolic follow up was not recommended. Repeat biochemical testing during this hospitalization revealed a normal acylcarnitine profile. The only abnormalities noted were a low proportion of acylcarnitine species from plasma, an elevated free-to-total carnitine ratio, and mild hypoketotic medium chain decarboxylic aciduria on urine organic acids. Gene sequencing of CPT1A revealed a novel homozygous splice site variant that confirmed his diagnosis. CPT1A deficiency has a population founder effect in the Inuit and other Arctic groups, but has not been previously reported in persons of Ashkenazi Jewish ancestry.
ARTICLE | doi:10.20944/preprints202107.0363.v1
Subject: Life Sciences, Other Keywords: omega-3; omega-6; fatty acids; camelina oil, flaxseed oil; canola oil; canine nutrition
Online: 15 July 2021 (18:17:06 CEST)
This study aimed to determine whether camelina oil is safe for use in canine diets, using canola oil and flax oil as controls as they are similar and generally regarded as safe (GRAS) for canine diets. Thirty privately-owned adult dogs of various breeds (17 females; 13 males), with an average age of 7.2 ± 3.1 years (mean ± SD) and body weight (BW) of 27.4 ± 14.0 were used. After a 4-week wash-in period using sunflower oil and kibble, dogs were blocked by breed, age, and size, and randomly allocated to one of three treatment oils (camelina (CAM), flax (FLX), or canola (OLA)) at a level of 8.2 g oil/100g total dietary intake. Body condition score (BCS), BW, food intake (FI), and hematological and select biochemical parameters were measured at various timepoints over a 16-week feeding period. All data were analyzed with ANOVA using PROC GLIMMIX of SAS. No biologically significant differences were seen between treatment groups for BW, BCS, FI, hematological and biochemical results. Statistically significant differences noted among some serum biochemical results were considered small and due to normal biological variation. These results support a conclusion that camelina oil is safe for use in canine nutrition.
Subject: Medicine & Pharmacology, Allergology Keywords: periodontal disease; non-alcoholic fatty liver disease; exercise; clinical trial; oral microbiota; saliva components
Online: 14 January 2021 (13:13:47 CET)
Exercise can be hypothesized to play an important role in NAFLD treatment by changing the oral bacterial flora and in the mechanism underlying periodontal disease. We performed salivary component analysis before and after an exercise regimen, and genome analysis of the oral bacterial flora to elucidate the underlying mechanism. Obese middle-aged men with NAFLD and periodontal disease were allocated to 12-week exercise (n=49) or dietary restriction (n=21) groups. We collected saliva to compare the oral microflora; performed predictive analysis of metagenomic functions; and measured the salivary immunoglobulin A, cytokine, bacterial lipopolysaccharide (LPS), and lactoferrin concentrations. The exercise group showed improvements in clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. Analysis of the microbial composition revealed that the numbers of Campylobacter (+83.9%), Corynebacterium (+142.3%), Actinomyces (+75.9%), and Lautropia (+172.9%) were significantly higher and that of Prevotella (−28.3%) was significantly lower. The findings suggest that an exercise regimen improves the oral environment of NAFLD patients by increasing the diversity of the oral microflora and reducing the number of periodontal bacteria that produce LPS and its capability.
ARTICLE | doi:10.20944/preprints202011.0492.v1
Subject: Materials Science, Biomaterials Keywords: 2D fatty liver in vitro model; Blu-Ray disc; Plasmonic Nanomaterials; Label-Free Biosensing
Online: 19 November 2020 (07:30:22 CET)
Non-alcoholic fatty liver (NAFLD) is a metabolic disorder related with a chronic lipid accumulation within the hepatocytes. This disease is the most common liver disorder worldwide and it is estimated that is present in up to 25% of the world's population. However, the real prevalence of this disease and the associated disorders is unknown mainly because reliable and applicable diagnostic tools are lacking. It is known that the level of albumin, a pleiotropic protein synthetized by hepatocytes, is correlated with the correct function of the liver. The development of a complementary tool that allow the direct, sensitive, and label-free monitoring of albumin secretion in hepatocyte cell culture can provide insight about the mechanism and drugs action in NAFLD. With this aim, we have developed a simple integrated plasmonic biosensor based on gold nanogratings from periodic nanostructures present in commercial Blu-ray optical disc. This sensor allows the direct and label-free monitoring of albumin in a 2D fatty liver disease model under flow conditions using highly specific polyclonal antibody. This technology avoids both the amplification and blocking steps showing a limit of detection within pM range (≈ 0.39 ng/mL). Thanks to this technology, we identified the optimal fetal bovine serum (FBS) concentration to maximize the lipid accumulation within the cells. Moreover, we discovered that at third day from lipids challenge, the hepatocytes increased the amount of albumin secreted. These data demonstrate the ability of hepatocytes to respond to the lipid stimulation releasing more albumin. Further investigation needed to unveil the biological significance of that cell behaviour.
REVIEW | doi:10.20944/preprints202011.0433.v1
Subject: Medicine & Pharmacology, Allergology Keywords: miRNAs; Obesity; Children; Non-alcoholic fatty liver disease; Type 2 diabetes mellitus; Endothelial dysfunction
Online: 16 November 2020 (15:44:40 CET)
Rising child obesity rate creates a need for tools quantifying metabolic changes in obese children and adolescents for purposes of comorbidities early detection or prevention. A candidate for such role seem to be miRNAs – in vivo serving as the suppressing factors of the gene expression. The aim of this study was to review the recent discoveries in this field and to conclude directions of research or application of studied molecules. Repeated browsing of databases, followed by screening for eligibility of results, led to final approval of 9 articles. Filtered studies examined the differences in miRNA (miR) expression levels of obese subjects and children suffering from obesity comorbidities. Studies concerning the endothelial dysfunction (ED) identified miR-630 as a possible treatment option. Search for the alternative markers in diagnosis of non-alcoholic fatty liver disease (NAFLD) suggested value of miR-199a-5p and miR-122. MiR-486, miR-146b and miR-15b may serve as a panel of markers grading the development of type 2 diabetes mellitus (T2DM) in children, although further research raised doubts in that matter. Another panel of miRNA molecules was indicated as useful in early detection of alterations leading to metabolic syndrome (MetS). No valid link between studied miRNAs and atherosclerosis (AS) was found. MiRNAs seem to be promising prognostic markers for the diagnosis of NAFLD, T2DM and MetS in children. Further studies are required to support these findings.
ARTICLE | doi:10.20944/preprints202008.0431.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: depressive disorder; omega-3 fatty acids; lipid profile; fluidity of membrane; children and adolescents
Online: 20 August 2020 (05:48:48 CEST)
Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids like total cholesterol (TCH), LDL- and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. This study aimed to investigate the relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities and erythrocyte membrane fluidity in 58 depressive children and adolescents, as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children's Depression Inventory (CDI), lipid profile by standard biochemical procedures, LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. We are the first to report that omega-3 FAs increase after 12 weeks of supplementation large HDL subfractions (anti-atherogenic) and decrease small HDL subfractions (pro-atherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder.
REVIEW | doi:10.20944/preprints201810.0166.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: FTO; liver; gluconeogenesis; lipogenesis; glucose; insulin; type 2 diabetes; non-alcoholic fatty liver disease
Online: 9 October 2018 (03:52:49 CEST)
Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed, but appears to have tissue-specific roles. Earlier studies have focused on the role of hypothlamic FTO in the regulation of metabolism. However, it appears that FTO plays a role in the regulation of metabolism in a tissue-specific manner. Recent studies suggest that expression of hepatic FTO is regulated by metabolic signals such as nutrients and hormones and altered FTO levels in liver affects glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.
ARTICLE | doi:10.20944/preprints201807.0613.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: tempeh; lactic acid bacteria; short chain fatty acids; metabolic syndrome; high fat diet; feces
Online: 31 July 2018 (09:37:51 CEST)
The increased consumption of high fat-containing foods has been linked to the prevalence of obesity and abnormal metabolic syndromes. Rhizopus oligosporus, a fungus in the family Mucoraceae, is widely used as a starter for homemade tempeh. Although R. oligosporus can prevent the growth of other microorganisms, it grows well with lactic acid bacteria (LAB). Lactobacillus plantarum can produce β-glucosidase, which catalyzes the hydrolysis of glucoside isoflavones into aglycones (with greater bioavailability). Therefore, the development of a soybean-based functional food by the co-inoculation of R. oligosporus and L. plantarum is a promising approach to increase the bioactivity of tempeh. In this study, the ameliorative effect of L. plantarum in soy tempeh on abnormal carbohydrate metabolism in high-fat diet (HFD)-induced hyperglycemic rats was evaluated. The co-incubation of L. plantarum with R. oligosporus during soy tempeh fermentation reduced the homeostatic model assessment of insulin resistance, HbA1c, serum glucose, total cholesterol, triglyceride, free fatty acid, insulin, and low-density lipoprotein contents and significantly increased the high-density lipoprotein content in HFD rats. It also increased the LAB counts as well as the bile acid, cholesterol, triglyceride, and short-chain fatty acid contents in the feces of HFD rats. Our results suggested that the modulation of serum glucose and lipid levels by LAB occurs via alterations in the internal microbiota, leading to the inhibition of cholesterol synthesis and promotion of lipolysis. Tempeh, produced with both L. plantarum and R. oligosporus, may be a beneficial dietary supplement for individuals with abnormal carbohydrate metabolism.
ARTICLE | doi:10.20944/preprints201712.0167.v1
Subject: Chemistry, Other Keywords: vegetable oils; emulsifiers; triglycerides; FAME; epoxidized fatty acids; glycerol; polyglycerol; PGPR; renewable raw materials
Online: 25 December 2017 (07:32:07 CET)
Oligo- and polyesters of polyglycerol and polyricinoleic acid are widely used as emulsifiers in various industries. Based on the condensation of glycerol and its oligomers with epoxidized derivatives of vegetable oils, new promising emulsifiers for oil-water systems were obtained. Complex structural and functional spectral analysis of synthesized substances showed that the main reactions leading to the formation of the desired products were the opening of epoxide cycles, the transesterification of esters and the condensation of fatty acid derivatives. The new combination of renewable raw materials is of undoubted interest for deeper vegetable oils chemical processing.
ARTICLE | doi:10.20944/preprints201711.0082.v1
Subject: Keywords: fatty hydroxamic acids; synthesis; spectroscopy; antioxidant activity; cytotoxic activity; biological targets; ADMET; safety profile
Online: 14 November 2017 (04:42:18 CET)
A fatty hydroxamic acid (FHA) mixture synthesized from olive oil triacylglycerides by hydroxylaminolysis and composed predominantly of oleyl and linoleyl hydroxamic acid (OHA and LHA, respectively) was characterized by means of IR, Raman, MS and 1D and 2D 1H- and 13C-NMR spectroscopy. The ratio of OHA and LHA (4:1) was confirmed by MALDI TOF/TOF mass spectrometry. The radical scavenging and the Fe2+-chelating activity, as well as antioxidant activity in β-carotene-linoleic acid and the Fe3+-reducing power assays of the FHAs yielded positive results. The results of FHA cell toxicity on normal fibroblast (BJ) and a tumour cell line (HeLa) revealed that the normal cell line was sensitive to FHAs within the entire range of applied concentrations (5 × 10−4 mg/mL to 5 × 10−1 mg/mL), while the HeLa tumour cell line was sensitive only at the highest FHA concentration (5 × 10−1 mg/mL). In silico target prediction indicated cannabinoid receptors 1 and 2, the fatty-acid amide hydrolase 1 and hystone deacetylases as the most probable targets of OHA and LHA. According to ADMET predictor analysis, the safety profiles of OHA and LHA are comparable to that of SAHA (vorinostat) the histone deacetylase inhibitor in use as an antineoplastic and immunomodulating agent.
ARTICLE | doi:10.20944/preprints202205.0081.v1
Subject: Life Sciences, Molecular Biology Keywords: fatty acid; RNAseq; transcriptome; immune response; Huntington's disease; metabolism; hepatic tissue; Longissimus lomborum; biomedical model
Online: 6 May 2022 (13:58:59 CEST)
The aim of this study was to identify the differentially expressed genes (DEG) from the skeletal muscle and liver samples of animal model for metabolic diseases in human. To perform the study, the fatty acid (FA) profile and RNA sequencing (RNA-Seq) data of 35 samples of liver tissue (SOY1.5, n=17 and SOY3.0, n=18) and 36 samples of skeletal muscle (SOY1.5, n=18 and SOY3.0, n=18) of Large White pigs were analyzed. The FA profile of the tissues was modified by the diet, mainly those related to monounsaturated (MUFA) and polyunsaturated (PUFA) FA. The skeletal muscle transcriptome analysis revealed 45 DEG (FDR 10%), and the functional enrichment analysis identified network maps related to inflammation, immune process, and pathways associated with the oxidative stress, type 2 diabetes and metabolic dysfunction. For the liver tissue, the transcriptome profile analysis revealed 281 DEG, which participate in network maps related to neurodegenerative diseases. With this nutrigenomics study, we verified that different levels of soybean oil in the pig diet, an animal model for metabolic diseases in humans, affected the transcriptome profile of skeletal muscle and liver tissue. These findings may help to better understand the biological mechanisms that can be modulated by the diet.
SHORT NOTE | doi:10.20944/preprints202111.0497.v1
Subject: Earth Sciences, Environmental Sciences Keywords: fatty acids; lipid content; invasive species; Kjeldahl; Gas chromatography; Integrated Multi Trophic Aquaculture; Pagasitikos Gulf
Online: 26 November 2021 (10:24:14 CET)
The total lipid and protein content of the invasive caprellid amphipod Caprella scaura, from the biofouling communities of fish farm cages in the Pagasitikos Gulf were analyzed and compared among seasons. Proteins were the most abundant component (48.5 – 49.3%). Lipid content was relatively lower, with a wider range (6.7 – 34%) and showed a distinct seasonal fluctuation with high values in the winter population and a gradual decrease in spring and summer, with the lowest values in Autumn. Composition of the fatty acids profile was consistent among the seasons, with palmitic (16:0), Oleic (18:1n-9), Eicosapentanoic (20:5n-3)(EPA) and Docosahexanoic acid (22:6n-3 )(DHA) being the most abundant fatty acids. The presence of high levels of EPA and DHA fatty acids makes the species a potential candidate for use of these organisms in aquaculture.