Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, are responsible for approximately 2.65 million deaths per year. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: 1) Supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; 2) Supplementation above the RDA, but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and 3) Public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.

Polyunsaturated fatty acids (PUFAs) and antioxidants are important mediators in the central nervous system (CNS). Lipid derivatives may be used to generate endocannabinoids or prostanoids derived from arachidonic acid, which attenuates excitotoxicity in quadripartite synapses with a focus in astrocytes and microglia; on the other hand, antioxidants, such as glutathione (GSH) and ascorbate, have been shown to signal through transmitter receptors and protect against acute and chronic oxidative stress, modulating the activity of different signaling pathways. Several authors have investigated the role of these nutrients in young and senescent brain, as well as in degenerative conditions such as Alzheimer’s and Parkinson's diseases. Through literature review, we aimed to highlight recent data on the role of fatty acids, antioxidants and physical activity in physiology and in molecular mechanisms of brain senescence. Data indicate the complexity and essentiality of endogenous/dietary antioxidants for maintenance of the redox status and control of neuroglial signaling under stress. Recent studies also indicate that omega-3 and -6 fatty acids act in a competitive manner to generate mediators for energy metabolism, feeding behavior, plasticity and memory mechanisms throughout aging. Finding pharmacological or dietary resources that mitigate or prevent neurodegenerative affections continues to be a great challenge and require additional efforts from researchers, clinicians and nutritionists in the field.

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.

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.

In this study, the olive pomace was considered because of its importance in the environment. So, this study carried out to estimate the total nitrogen content and the fatty acids profile of olive pomace. The olive pomace samples were collected from Irbid, Jarash, Ajloun and Mafraq during the harvesting season 2014 to study the biochemical characteristics of fatty acid composition and the total nitrogen (TN) content. The total nitrogen content was determined by standard Kjeldahl method and the fatty acid profile was detected by gas chromatography (GC). The results show that the total nitrogen content ranged from (0.39 ± 0.0) to (0.62 ± 0.02) with statistically significant difference suggesting that the composition of matrices and their percentage may be responsible for composition of amendments. The calculated total protein percentage ranged between (2.43 ± 0.00) to (3.87 ± 0.17). Also, 13 different fatty acids were quantitatively profiled and quantitated. Oleic acid (C 18:1) was found to be the highest percentage of all other fatty acids and ranged between (59.03%) and (63.81%), moreover the C 18:1/C 18:2 (oil quality) was calculated and C.V% showed variation meaning that nutritional implication could affect the oxidative stability of oils. In conclusion, OP by-product could give a sustainable and alternative-cheap source for fertilizers, pharmaceutical industries, cosmetics and other industries.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-treatment as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an anti-inflammatory effect of B. subtilis, manifested as a decrease in immune cell populations within the basal state along with an increase in anti-inflammatory immune cells in response to LPS stimulation. Overall gastrointestinal health, microbiota, and circulating and fecal markers of inflammation and gut barrier function were largely unaffected by DE111 treatment. These data suggest that the novel probiotic B. subtilis DE111 may have clinical applications in modulating immune homeostasis via anti-inflammatory mechanisms.

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.

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.

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 C_18:0 ﹤ C_18:2 ≈ C_16:0 ﹤ C_18:1; 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.

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.

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.

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.

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.

Since coffee has been shown to influence positively the metabolism of subjects with metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control but improved fed hyperinsulinemia and HOMA-IR, and plasma adiponectin levels. The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating and intrahepatocellular alanine transaminase activity, assessed by hyperpolarized-¹³C NMR spectroscopy, were reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

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.

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.

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.

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.

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.

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.

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.

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.

The aim of this study was to develop a basic model to predict enteric methane emission from dairy cows and to update operational calculations for the national inventory in Norway. Basic models were developed using a database with 63 treatment means from 19 studies. The database included records for enteric CH4 production (MJ/day), dry matter intake (DMI), and dietary nutrient composition. The basic models were evaluated against an external database (n=36, from ten studies) along with other extant models. When evaluated by low root mean square prediction errors and high concordance correlation coefficients, the developed basic models that included DMI, dietary concentrations of fatty acids and neutral detergent fiber performed slightly better in predicting CH4 emissions than extant models. In order to propose country-specific values for the CH4 conversion factor Ym (% of gross energy intake partitioned into CH4) and thus to carry out the national inventory for Norway, the existing operational model was updated for the prediction of Ym over a wide range of feeding situations using energy corrected milk and dietary concentrate share as predictor variables. Input values of Ym were updated based on the results from the basic models. The predicted Ym ranged from 6.22 to 6.72%. In conclusion, the prediction of CH4 production from dairy cows was improved with the help of newly published data, which enabled an update of the operational model for calculating the national inventory of CH4 in Norway.

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.

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.

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.

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.

Ataxin-2 (ATXN2) acts during stress-responses, modulating mRNA translation and nutrient metabolism. Atxn2 knockout mice exhibit progressive obesity, dyslipidemia and insulin resistance. Conversely, the progressive ATXN2 gain-of-function due to polyGlutamine (polyQ) expansions leads to a dominantly inherited neurodegenerative process named spinocerebellar ataxia type 2 (SCA2), with early adipose tissue loss and late muscle atrophy. We tried to understand lipid dysregulation in a SCA2 patient brain and in an authentic mouse model. Thin layer chromatography of a patient cerebellum was compared to the lipid metabolome of Atxn2-CAG100-KnockIn (KIN) mouse spinocerebellar tissue. The human pathology caused deficits of sulfatide, galactosylceramide, cholesterol, C22/24-sphingomyelin and gangliosides GM1a/GD1b, despite quite normal levels of C18-sphingomyelin. Cerebellum and spinal cord from the KIN mouse showed a consistent decrease of various ceramides, with a significant elevation of sphingosine in the more severely affected spinal cord. Deficiency of C24/26-sphingomyelins contrasted with excess C18/20-sphingomyelin. Spinocerebellar expression profiling revealed consistent reductions of CERS protein isoforms, of Sptlc2 and Smpd3, but upregulation of Cers2 mRNA, as prominent anomalies in the ceramide-sphingosine metabolism. Reduction of Asah2 mRNA correlated to deficient S1P levels. In addition, downregulations for the elongase Elovl1, Elovl4, Elovl5 mRNAs and ELOVL4 protein explain the deficit of very-long-chain sphingomyelin. Reduced ASMase protein levels correlated to the accumulation of long-chain sphingomyelin. Overall, a deficit of myelin lipids was prominent in SCA2 nervous tissue at prefinal stage, not compensated by transcriptional adaptation of several metabolic enzymes. Myelination is controlled by mTORC1 signals, so our human and murine observations are in agreement with the known role of ATXN2 yeast, nematode and mouse orthologs as mTORC1 inhibitors and autophagy promoters.

Fatty acids (FAs) represent an important class of metabolites, impacting on membrane building blocks and cellular regulatory networks. In nature, prokaryotes are characterized with the most impressing FA structural diversity and the highest relative contents of free fatty acids (FFAs). Thereby, nitrogen-fixing bacteria (order Rhizobiales), often found in symbiosis with legumes, attract a special interest. Indeed, FAs impact on the structure of rhizobial nodulation factors, required for successful infection of plant root. Although the FA patterns can be addressed by GC- and LC-MS, these methods are time-consuming and suffer from compromised sensitivity, low stability of derivatives and artifacts. In contrast, MALDI-TOF-MS represents an excellent platform for high-efficient metabolite fingerprinting, also applicable to FFAs. Therefore, here we propose a simple and straightforward protocol for high-throughput relative quantification of FFAs in rhizobia by the combination of Langmuir technology and MALDI-TOF-MS, which is featured with high sensitivity, accuracy and precision of quantification. Here we propose a step by step procedure comprising rhizobia culturing, pre-cleaning, extraction, sample preparation, mass spectrometric analysis, data processing and post-processing. To demonstrate the analytical potential of the protocol we illustrate it by a case study – comparison the FFA metabolomes of two rhizobia species - Rhizobium leguminosarum and Sinorhizobium meliloti.

Nowadays, the fingerprinting methodologies of olive oils are dominated. They consider the entire analytical signal, which is acquired and recorded by the analytical instrument, directly from olive oil or isoleted fraction, i,e chromatogram. The shape and intensity of the recorded signal the instrumental fingerprint from the whole olive oil adulteration. Therefore, the methodolygy is based on the chemical composition (Fatty acids and Triglycerides compositions). However, Fatty acids composition as an indicator of purity suggests that linolenic acid content could be used as a parameter for the detection of extra virgin olive oil fraud with 5% of soybean oil. The adulteration could also be detected by the increase of the trans-fatty acid contents with 3% of soybean oil, 2% of corn oil and 4% of sunflower oil. The use of the ∆ECN42 proved to be effective in the Chemlali extra-virgin olive oil adulteration even at low levels: 1% of sunflower oil, 3% of soybean oil and 3% of corn oil. Therefore, compared to classical methods PCA and new approach of using LDA application could represent an alternative and innovative tool for faster and cheaper evaluation of extra-virgin olive oil adulteration.

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.

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to exert major effects on the immune system, both in vivo and in vitro. This interaction is clearly linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on carefully studied animal models. Microbial-immune system crosstalk has been linked to short chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multi-organ inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.

Platelets have long been associated with sustaining the balance between hemostasis and thrombosis. Platelets, however, are also involved in a wide range of biological activities, including inflammation, immunology, wound healing, cancer biology, and angiogenesis. Platelets' diverse roles are mediated by the expression of various adhesive and immune receptors and the secretion of a diverse array of bioactive proteins, ions stored in granules, and several lipid mediators. Platelets also release pro-inflammatory and anti-inflammatory, and angiogenic factors and shed microparticles into the bloodstream. The challenge for therapeutic intervention in non-hemostatic disease is identifying the factors that primarily inhibit specific targets implicated in platelets' complicated contribution to inflammation or tumor growth while leaving their hemostatic function intact. In addition, blood platelets are involved in infection and innate and adaptive immunity by mediating complicated vascular homeostasis via specialized receptors and granule release, RNA transfer, and mitochondrial secretion. Anti-platelet drugs/bioactive compounds are developed based on their platelet anti-aggregatory properties; however, very little information is available on their effects on non-hemostatic function. Therefore, a better understanding of the impact of the anti-platelet bioactive on the platelets' diverse roles and mechanisms may help develop new strategies and prevent CVD and other diseases. In this review, a comprehensive overview of platelet multifunctional roles in CVD and other diseases and dietary factors' modulatory effects are described.

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.

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.

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.

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.

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.

The aim of this work was the study and evaluation of winery by-products in the framework of circular bioeconomy. Grape seeds and grape skins from Greek traditional Ionian Islands varieties were analyzed in an attempt to provide the appropriate basis for model development of their sustainable exploitation at a local or regional level. The wastes collected directly from the wineries immediately after the vinification process and analyzed by chromatographic and spectroscopic techniques. Also, annual production and yields were estimated. Grape seed oil quality was evaluated based on fatty acid methyl esters (FAMEs) composition. Grape skins phenolic fraction was extracted by an eco-friendly, non-toxic water-glycerol solvent system and were detected qualitatively. Also, total phenolic content (TPC) and antioxidant activity were measured. Based on estimated yields, our results demonstrate that winery by-products have the potential to promote the cyclical bioeconomy in a modern economic growth model that will reduce waste, and environmental costs as they can be reused as whole material in foods, dietary supplements, cosmetic ingredients, food colorants and preservatives.

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.

Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of leptin receptor signalling. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.

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.

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.

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.

This study aimed to characterize the long non-coding RNA (lncRNA) expression in the bovine mammary gland and to infer their functions in dietary response to 5% linseed oil (LSO) or 5% safflower oil (SFO). Twelve cows (six per treatment) in mid lactation were fed a control diet for 28 days followed by a treatment period (control diet supplemented with 5% LSO or 5% SFO) of 28 days. Mammary gland biopsies were collected from each animal on day-14 (D-14, control period), D+7 (early treatment period) and D+28 (late treatment period) and were subjected to RNA-Sequencing and subsequent bioinformatics analyses. Functional enrichment of lncRNA was performed via potential cis regulated target genes located within 50 Kb flanking regions of lncRNAs and having expression correlation of >0.7 with mRNAs. A total of 4955 lncRNAs (325 known and 4630 novel) were identified which potentially cis targeted 59 and 494 genes in LSO and SFO treatments, respectively. Enrichments of cis target genes of lncRNAs indicated potential roles of lncRNAs in immune function, nucleic acid metabolism and cell membrane organization processes as well as involvement in Notch, cAMP and TGF-β signaling pathways. Thirty-two and 21 lncRNAs were differentially expressed (DE) in LSO and SFO treatments, respectively. Six genes (KCNF1, STARD13, BCL6, NXPE2, HHIPL2 and MMD) were identified as potential cis target genes of six DE lncRNAs. In conclusion, this study indicated potential roles for lncRNAs in mammary gland immune functions and development and provided potential candidate genes and pathways via which lncRNAs can function in diet responses.

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.

The most common liver disorder nowadays is non-alcoholic fatty liver disease(NAFLD) and it is a progressive disease that rises in severity from steatosis to nonalcoholic steatohepatitis(NASH), fibrosis and cirrhosis to increase risk of developing hepatocellular carcinoma. It is a cause of great concern as there is an estimated seventy million Americans who are currently affected by NAFLD, and this is expected to only increase because of its association with obesity and diabetes and also a lack of therapies to keep its development and progression in check. In this particular study we performed a gene set enrichment analysis(GSEA) of differentially expressed genes in a green tea against methionine-choline deficient diet in high-fat patients in the development of non-alcoholic fatty liver disease(NAFLD). The downregulated genes were used to perform an enrichment analysis and in the ARCHS4 TFs Coexpression database the most significant gene was found to be KLF5_human_tf_ARCHS4_coexpression. In the ARCHS4 Kinases Coexpression pathway database STYK1_human_kinase_ARCHS4 Coexpression was found to be the most significant gene. And finally for the upregulated genes a similar enrichment analysis was performed and in the humancy database γ-linolenate biosynthesis_Homo sapiens_PWY-6000 gene was discovered to be the most significant one. This study has used bioinformatics tools and the Enrichr software to perform a comparative analysis of differentially expressed gene sets for high-fat patients having a diet consisting of green tea against a methionine-choline deficient diet. Green tea is known to contain several antioxidants and polyphenols which provide protection against many liver diseases such as non-alcoholic fatty liver disease(NAFLD). The present study simply tries to build awareness of this to the general public and allow them to learn more about certain diets which have protective effects against liver diseases. Hopefully by implementing these in their daily lifestyles the public can gain some form of protection against these types of liver disorders.

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.

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.

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.

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.

We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms behind these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12-weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM.

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 &lt; 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.

Literature is inconsistent as to how coffee affects the features of the metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. We aimed to compare the in-vivo effects of unfiltered coffee with a selected mixture of its compounds on diet-induced MetS. 24 male Sprague-Dawley rats were fed a high-fat (35% W/W) food plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water in a dosage equal to 4 cups/day in a human. Compared to the controls, only coffee supplementation decreased total food intake, weight gain, and estimated average plasma glucose. Surrogate measures of insulin resistance (fasting insulin, HOMA-IR, and oral glucose tolerance) were improved at endpoint in the coffee group. Circulating triglyceride levels were also reduced by coffee. Histopathological and quantitative measurements indicated lower grades of liver steatosis after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

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.

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.

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.

Maternal milk, from well-nourished and healthy mothers, is a source of several bioactive compounds and balanced nutrients required for proper growth and development of the infant. Hence it is regarded as the optimal form of nourishment. Human milk fat from human milk is the most crucial component and is a necessity for the growing infant. However, in certain cases, the breast milk may fulfill the nutritional needs or the breast-feeding of the infant is not feasible; infant formulae are then considered as the best alternative as nutritional support. It becomes essential for the infant formula to behave and provide nutritive support in the same way as human milk. In order to achieve so, the most crucial components of all should also be prepared precisely, i.e., the analogue of human milk fat. This analogue, which mimics the actual human milk fat, can be then used as a prime ingredient while designing the infant formula. Significant research and several advances have been made in preparing the infant formula enriched with adequate fat content, and more studies are still being conducted in order to achieve a more sound product in the most economical and simplest way possible.

Infectious as well as most non-infectious diseases share certain common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors, produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, they produce metabolic alterations that influence the pathogenesis of the disease. In this review we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, which induces migration and infiltration of immune cells in target tissues, and is involved in disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

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.

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.

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.

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.

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).

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.

The evolutionary success of land plants largely relies on their ability to cope with constant environmental fluctuations, which negatively impact their reproductive fitness and trigger adaptational responses to biotic and abiotic stresses. In this challenging scenario, comprehensive research efforts so far aimed at depicting the roles of well-known phytohormones, mainly auxins, along with brassinosteroids, jasmonates, and abscisic acid, although the signaling networks coordinating the crosstalk among them remains vaguely understood. Accordingly, this review focuses on the Arabidopsis Amidase Signature (AS) superfamily members, highlighting the hitherto relatively underappreciated functions of AMIDASE1 (AMI1) and FATTY ACID AMIDE HYDROLASE (FAAH), as crucial coordinators of the growth-defense response trade-off by modulating auxin and ABA homeostasis.

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).

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.

A new pathway leading to the n-10 fatty acid series has been recently evidenced, starting from sapienic acid - a monounsaturated fatty acid (MUFA) resulting from the transformation of palmitic acid by delta-6 desaturase. Sapienic acid attracts attention as novel marker of cancer cell plasticity. Here, we analyzed fatty acids including the n-10 fatty acid contents, and compared for the first time cell membranes and the corresponding extracellular vesicles (EV) of two human prostatic adenocarcinoma cell lines of different aggressiveness (PC3 and LNCaP). The n-10 components were 9-13% of the total fatty acids in both cancer cell lines and EVs, with total MUFA levels significantly higher in EVs of the most aggressive cell type (PC3). High sapienic/palmitoleic ratios indicated the preference for delta-6 vs. delta-9 desaturase enzymatic activity in these cell lines. The expressions analysis of enzymes involved in desaturation and elongation by qRT-PCR showed a higher desaturase activity in PC3 and a higher elongase activity toward polyunsaturated fatty acids than toward saturated fatty acids, compared to LNCaP cells. Our results improve the present knowledge in cancer fatty acid metabolism and lipid phenotypes, highlighting EV lipidomics to monitor positional fatty acid isomer profiles and MUFA levels in cancer.

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.

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.

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).

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.

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.

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.

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.

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.

A genome-wide association study (GWAS) was performed on a set of 260 lines which belong to three different bi-parental flax mapping populations. These lines were sequenced to an averaged genome coverage of 19× using the Illumina Hi-Seq platform. Phenotypic data for 11 seed yield and oil quality traits were collected in eight year/location environments. A total of 17,288 single nucleotide polymorphisms were identified, which explained more than 80% of the phenotypic variation for days to maturity (DTM), iodine value (IOD), palmitic (PAL), stearic, linoleic (LIO) and linolenic (LIN) acid contents. Twenty-three unique genomic regions associated with 33 QTL for the studied traits were detected, thereby validating four genomic regions previously identified. The 33 QTL explained 48-73% of the phenotypic variation for oil content, IOD, PAL, LIO and LIN but only 8-14% for plant height, DTM and seed yield. A genome-wide selective sweep scan for selection signatures detected 114 genomic regions that accounted for 7.82% of the flax pseudomolecule and overlapped with the 11 GWAS-detected genomic regions associated with 18 QTL for 11 traits. The results demonstrate the utility of GWAS combined with selection signatures for dissection of the genetic structure of traits and for pinpointing genomic regions for breeding improvement.

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.

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.

Metabolic disorders, metabolic syndrome and non-alcoholic fatty liver disease, and depression are those of the most common and debilitating disorders worldwide that often coexist further increasing mortality risks. Although the exact mechanisms underlying this association are poorly known, several hypotheses have been proposed: antipsychotic medication and antidepressants use, diet and physical activity or any other lifestyle factors. However, the high co-occurrence rate of depression and metabolic disorders suggests a possible pathophysiological overlap. In this paper I review several raised mechanisms for this overlap which are the hypothalamic-pituitary-adrenal axis dysregulation, immune alterations with chronic inflammation, as well as oxidative stress. In my view, there is one common thread running through all the aforementioned areas of pathophysiology which is microbiota alteration. So far, several possible interventions in our microbiota have been introduced into clinical practice - dietary and other lifestyle changes, supplementation with prebiotics or probiotics, fecal microbiota transplantation – but with vague indications. A better characterization of the above associations may represent a critical step at phenotyping, and a more targeted approach to the treatment of both depressive and metabolic disorders. At the end of the paper, I give several practical applications for future studies.

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.

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.

Compelling epidemiologic data support the critical role of dietary fructose in the epidemic of obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). The metabolic effects of fructose on the development of metabolic syndrome and NAFLD are not completely understood. High fructose intake impairs copper status, and copper-fructose interactions have been well documented in rats. Altered copper-fructose metabolism leads to exacerbated experimental metabolic syndrome and NAFLD. A growing body of evidence has demonstrated that copper levels are low in NAFLD patients. Moreover, hepatic and serum copper levels are inversely correlated with the severity of NAFLD. Thus, high fructose consumption and low copper availability are considered two important risk factors in NAFLD. However, the causal effect of copper-fructose interactions as well as the effects of fructose intake on copper status remain to be evaluated in humans. The aim of this review is to summarize the role of copper-fructose interactions in the pathogenesis of the metabolic syndrome and discuss the potential underlying mechanisms. This review will shed light on the role of copper homeostasis and high fructose intake and point to copper-fructose interactions as novel mechanisms in the fructose induced NAFLD.

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.

Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer Disease will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed focussing on Alzheimer Disease pathogenesis.

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.

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.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged >=65 years in developed countries. Globally, it affects 30-50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many observational studies, such as AREDS-1 and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high fat and high glucose or fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

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.

Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0 activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway. To assess the potential for C15:0 to enhance processes associated with longevity and healthspan, we used human cell-based molecular phenotyping assays to compare C15:0 with three longevity-enhancing candidates: acarbose, metformin, and rapamycin. C15:0 (n=36 activities in 10 of 12 cell systems) and rapamycin (n=32 activities in 12 of 12 systems) had the most clinically relevant, dose-dependent activities. At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFɑ, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds.