Metabolic disorders have become among the most serious threats to human health, leading to severe chronic diseases such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, as well as cardiovascular diseases. Interestingly, despite the fact that each of these maladies has different physiological and clinical symptoms, they appear to share certain pathological traits such as intracellular stress and inflammation induced by metabolic derangements stemmed from over nutrition frequently aggravated by modern sedentary life style. These modern ways of living inundate cells and organs with saturating levels of sugar and fat, leading to glycotoxicity and lipotoxicity that induce intracellular stress signaling ranging from oxidative to ER stress response to cope with the metabolic insults [1]. In this review, we discuss the roles played by cellular stress and its responses in shaping metabolic disorders. We have summarized here current mechanistic insights explaining the pathogenesis of these disorders. These are followed by a discussion of the latest therapies targeting the stress response pathways.

Ultraviolet (UV) radiation has both harmful and beneficial effects on human health. It can cause skin damage and cancer, but also provides the primary source of vitamin D. Additionally, UV radiation affects energy metabolism in mice with metabolic diseases and has protective effects on hypertension and cardiovascular diseases.Metabolic Syndrome is a collection of metabolic dysfunctions such as dyslipidemia, hypertension, hyperglycemia, abdominal/central obesity, and insulin resistance. Chronic UVR exposure suppressed obesity and type 2 diabetes in high-fat diet-fed mice, while vitamin D supplementation did not replicate these effects. On the other hand, topical application of nitric oxide (NO) donors replicated UV effects on mice, and NO scavengers prevented the positive impact of UV. UVR may prevent the development of obesity and metabolic syndrome through mechanisms that depend on UVR-induced NO, not vitamin D. Exposure to sunshine has a protective impact on blood pressure and cardiovascular disease. Although lower vitamin D concentration is linked to increased hypertension and the incidence of CVD, oral vitamin D supplementation does not decrease blood pressure or the risk of CVD, indicating that vitamin D may not mediate the beneficial effects of sun exposure. Instead, NO plays a crucial role as an endogenous vasodilator, produced by the vascular endothelium. Solar UVA may release nitrogen oxides from skin storage into the bloodstream, lowering blood pressure and cardiovascular mortality.In conclusion, UVR exposure could be a promising non-pharmacological intervention for metabolic syndrome, hypertension, and CVD prevention, and NO may play a crucial role in mediating these effects. Further research is needed to explore the precise mechanisms and identify the optimal doses and exposure times of UVR.

Modern research achievements support health-promoting effects of natural products and diets rich in polyphenols. Pomegranate (PG) (Punica granatum L.) contain a considerable number of bioactive compounds that exert a broad spectrum of beneficial biological activities, including antimicrobial, antidiabetic, antiobesity, and atheroprotective properties. In this view, the reviewed literature shows that PG intake might reduce insulin resistance, cytokine levels, redox gene expression, blood pressure elevation, vascular injuries and lipoprotein oxidative modifications. Lipid parameters corrective capabilities of PG-ellagitannins are also sufficiently reported to be significantly effective in reducing hyperlipidemia (TC, LDL-C, VLDL-C, and TAGs), plasma HDL-C concentrations, TC/HDL-C and LDL-C/HDL-C ratio. The health benevolent effects of pomegranate consumption appear to be produced through the amelioration of adipose tissue endocrine function, fatty acid utilization, GLUT receptor expression, paraoxonase activity enhancement, PPAR and NFκB modulation. Although the results from animal experiments are encouraging, human findings published in this field are inconsistent and still limited in many points of view. The present review discusses and provides a critical analysis of PG's bioeffects on metabolic syndrome components, type-2 diabetes, obesity, and dyslipidemia, as well as on some cardiovascular-related diseases. A brief overview of the pharmacokinetic properties, safety, and bioavailability of PG-ellagitannins is also included.

This study aimed to report the magnitude of modifiable lifestyle factors, their relationships with metabolic disorders in Burkinabè adults by using nationally representative data. This cross-sectional study included 4100 adults selected through multistage cluster sampling performed during the first national survey conducted in 2013 in Burkina Faso. The modifiable factors we considered were tooth cleaning, fruit and/or vegetable (FV) intake, substances’ use, physical activity and overweight/obesity, while metabolic syndrome abnormal components defined metabolic disorders. We performed logistic regressions. 31.1% cleaned the teeth at least twice a day, 14.7% consumed five or more FV, 39.7% used alcohol and/or tobacco, the prevalence of physical inactivity and overweight/obesity was respectively 6.6% and 17.7%. About 41.0% had at least two metabolic disorders and 9.5% had at least three. Lifestyle factors associated with having at least two metabolic disorders were overweight/obesity, more FV intake (when five or more aOR=1.5, p<0.001), physical inactivity (aOR=1.3, p<0.05), tooth cleaning (aOR=0.8, p<0.01). Except for consuming five or more FV (aOR=1.4, p=0.09), the same trend of relationships was observed with having at least three metabolic disorders. Excluding overweight/obesity and physical inactivity, unhealthy modifiable lifestyle factors were common and tooth cleaning was found as a protective practice for metabolic disorders.

Background: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). Increased levels of reactive oxygen and nitrogen species (RONS) and nitro-oxidative stress toxicity (NOSTOX) partially underpin this comorbidity.Aims: To examine the associations of RONS/NOSTOX biomarkers with MetS after adjusting for the significant effects of mood disorders (major depression, and bipolar type 1 and 2), generalized anxiety disorder (GAD), tobacco use disorder (TUD), and male sex.Methods: The study included subjects with (n=65) and without (n=107) MetS and measured levels of superoxide dismutase 1 (SOD1), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) and computed z unit-weighted composite scores which reflect RONS/NOSTOX. The study included 105 patients with mood disorders, 46 with GAD, and 95 with TUD.Results: MetS was associated with increased levels of MDA and AOPP, independently from mood disorders, TUD, sex and GAD. Atherogenicity and insulin resistance (IR) were significantly associated with a NOSTOX composite score. Mood disorders, TUD, GAD, male sex and MetS independently contribute to increased RONS/NOSTOX. The RONS/NOSTOX profile of MetS was different from that of GAD, which showed increased SOD1 and NOx levels. TUD was accompanied by increased SOD1, LOOH and MDA, and male sex by increased LOOH and AOPP.Conclusions: MetS is characterized by increased lipid peroxidation with aldehyde formation and chlorinative stress, and atherogenicity and IR are strongly mediated by RONS/NOSTOX. Partially shared RONS/NOSTOX pathways underpin the comorbidity of MetS with mood disorders, GAD, and TUD.

Methylglyoxal (MGO) is the major compound belonging to reactive carbonyl species (RCS) responsible for the generation of advanced glycation end products (AGEs). Its upregulation followed by deleterious effects at the cellular and systemic level is associated with metabolic disturbances (hyperglycemia/hyperinsulinemia/insulin resistance/hyperlipidemia/inflammatory processes/carbonyl stress/oxidative stress/hypoxia). Therefore, it is implicated in a variety of disorders including metabolic syndrome, diabetes mellitus and cardiovascular diseases. In this review an interplay between pathways leading to MGO generation and scavenging is addressed, in regard to this system’s impairment in pathology. The issues associated with mechanistic MGO involvement in pathological processes, as well as the discussion on its possible causative role in cardiometabolic diseases are enclosed. Finally, the main strategies aimed at MGO and its AGEs downregulation with respect to cardiometabolic disorders treatment are addressed. Potential glycation inhibitors and MGO scavengers are discussed, as well as the mechanisms of their action.

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.

Novel cultivation technologies demand the adaptation of existing analytical concepts. Metabolic flux analysis (MFA) requires stable-isotope labeling of biomass-bound protein as the primary information source. Obtaining the required protein in cultivation set-ups where biomass is scarce or inaccessible due to low cell densities and cell immobilization is difficult to date. We developed a non-disruptive analytical concept for 13C-based metabolic flux analysis based on secreted protein as an information carrier for isotope mapping in the protein-bound amino acids. This "metabolic flux probe" (MFP) concept was investigated in different cultivation set-ups with a recombinant, protein-secreting yeast strain. The obtained results grant insight into intracellular protein turnover dynamics. Experiments under metabolic but isotopically nonstationary conditions in continuous glucose-limited chemostats at high dilution rates demonstrated faster incorporation of isotope information from labeled glucose into the recombinant reporter protein than in biomass-bound protein. Our results suggest that the reporter protein was polymerized from intracellular amino acid pools with higher turnover rates than biomass-bound protein. The latter aspect might be vital for 13C-flux analyses under isotopically nonstationary conditions for analyzing fast metabolic dynamics.

Hydrogen is useful as a fuel and could be produced by a variety of means. One approach uses artificial photosynthesis where energy from sunlight powers the splitting of water into hydrogen and oxygen. But, biological methods for producing hydrogen has emerged strongly over the past decades. In particular, specific microorganisms could use different substrates to produce hydrogen at differing yields. Such fundamental discoveries with industrial applications thus motivated the use of metabolic engineering approaches and methodologies in enhancing biological hydrogen production through a series of enzyme over-expression, pathway debottlenecking, and gene deletion. However, such approaches heavily rely on the selection of an appropriate microbial chassis for biohydrogen production. With the proper strain in hand, use of alternative substrates may engender greater hydrogen productivities. But learning from the bioprocessing field, co-culture of two compatible microorganisms have been sought after for improving biohydrogen production. In addition, thermophilic microbes may also be useful candidates for exploiting hydrogen production from composting. Future outlook in the field looks into filling our gaps in understanding of the metabolic network that feeds into hydrogen production in different organisms. But, more importantly, problems such as reduced growth rate in engineered microbes point to fundamental issues with using genetically engineered microorganisms for improved biohydrogen production, to which clever bioprocess engineering may yield solutions.

Cell free systems are a widely used research tool in systems and synthetic biology and a promising platform for manufacturing of proteins and chemicals. In the past, cell free biology was primarily used to better understand fundamental biochemical processes. Notably, E. coli cell free extracts were used in the 1960s to decipher the sequencing of the genetic code. Since then, the transcription and translation capabilities of cell free systems have been repeatedly optimized to improve energy efficiency and protein yield. Today, cell free systems, in combination with the rise of synthetic biology, have taken on a new role as a promising technology for just in time manufacturing of therapeutically important biologics and high-value small molecules. They have also been implemented in an industrial scale for the production of antibodies and cytokines. In this review, we discuss the evolution of cell free systems, advancements in cell free protein synthesis, and cell free metabolic engineering, and conclude with discussing the importance and feasibility of mathematical modeling in cell free systems.

(1) Background: Metabolic syndrome is a strong predictor of cardiovascular disease thus the objective of the study was to verify the prevalence of metabolic syndrome in farmers, as well as to verify the association with sociodemographic, work and lifestyle factors. (2) Methods: Cross-sectional, observational study, carried out with 790 individuals. For the diagnosis of metabolic syndrome, the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) and International Diabetes Federation (IDF) criteria were used. Pearson's chi-square test and binary logistic regression were used to verify factors associated with metabolic syndrome (3) Results: The prevalence of MS according to the IDF criteria was 16.3% overall, with 9.7% of women (95% CI: 6.66–16.16) and 6.6% of men (95% CI: 5.17–11.97). According to the NCEP/ATP III criterion, it was 12.3% overall, with 7.5% corresponding to women (95% CI: 6.62 – 13.13) and 4.8% to men (95% CI: 3.5 – 8.70). With regard to the conditions that make up metabolic syndrome, it was found that high density lipoprotein, high blood pressure and high waist circumference were the most prevalent. (4) Conclusions: The prevalence of metabolic syndrome is considerable in the population when compared to other regions, both rural and urban, in Brazil.

Kidney disease is a significant health problem worldwide, affecting an estimated 10% of the global population. Kidney disease encompasses a diverse group of disorders that vary in their underlying pathophysiology, clinical presentation, and outcomes. These disorders include acute kidney injury (AKI), chronic kidney disease (CKD), glomerulonephritis, nephrotic syndrome, polycystic kidney disease, diabetic kidney disease, and many others. Despite their distinct etiologies, these disorders share a common feature of immune system dysregulation and metabolic disturbances. The immune system and metabolic pathways are intimately connected and interact to modulate the pathogenesis of kidney diseases. The dysregulation of immune responses in kidney diseases includes a complex interplay between various immune cell types, including resident and infiltrating immune cells, cytokines, chemokines, and complement factors. These immune factors can trigger and perpetuate kidney inflammation, causing renal tissue injury and progressive fibrosis. In addition, metabolic pathways play critical roles in the pathogenesis of kidney diseases, including glucose and lipid metabolism, oxidative stress, mitochondrial dysfunction, and altered nutrient sensing. Dysregulation of these metabolic pathways contributes to the progression of kidney disease by inducing renal tubular injury, apoptosis, and fibrosis. Recent studies have provided insights into the intricate interplay between immune and metabolic pathways in kidney diseases, revealing novel therapeutic targets for the prevention and treatment of kidney diseases. Potential therapeutic strategies include modulating immune responses through targeting key immune factors or inhibiting pro-inflammatory signaling pathways, improving mitochondrial function, and targeting nutrient-sensing pathways such as mTOR, AMPK, and SIRT1. This review highlights the importance of the interplay between immune and metabolic pathways in kidney diseases and the potential therapeutic implications of targeting these pathways.

The increasing need for effective analytical tools to evaluate beef quality has prompted the development of new procedures to improve the animal sector’s performance. In this study, three beef breeds—Thai native (TN), crossbred Brahman x Thai native (BT), and crossbred Charolais x Brahman (CB)—were compared in terms of their physicochemical and metabolic profiles. The findings demonstrated that TN beef was lighter and tougher than other beef. Beef odor was stronger in BT. In addition, CB beef was the most tender and the highest intramuscular fat content. Twenty-one different metabolites were found overall through NMR and chemometric approaches. High levels of lactate and creatine were found in all species. The primary factors contributing to the difference in OPLS-DA loading plots were acetylcholine, valine, adenine, leucine, and phosphocreatine, β-hydroxypyruvate, ethanol, adenosine diphosphate, creatine, acetylcholine, and lactate. The multivariate analysis indicated that these metabolites in beef cattle breeds could be distinguished using NMR spectroscopy. The results of this study provide valuable information on the quality and meat metabolites in different breeds. This could help in the development of a more accurate assessment of the quality of beef in future research.

In the last decade, different omic technologies have experiences an exponential technological advancement. However, metabolomics has not followed a similarly vertiginous improving improvement and are far from genomics or transcriptomics in terms of throughput, cost and even accuracy. Therefore, genome-scale in-silico methodologies to estimate metabolic activities from genomic data constitute an active field. The solutions available fall into two extremes: those with few assumptions about the relationships among proteins and metabolites, which are easy-to-use but less accurate and those that account for the complex relationships among molecules and proteins defined in the metabolic pathways, which are more accurate but require mathematical skills. Here, we introduce Metabolica, an algorithm that considers the complex functional relationships among all the molecules and proteins involved in the metabolic pathway analyzed but keeping an easy use that do not require of advanced mathematical skills. Metabolica has been implemented in a freely available software R package. The software inputs transcriptomic data and infers the activities of the reactions that produce the different metabolites in the pathway analyzed. An example shows how detected dysregulated metabolites in several cancers are related to patient survival.

Inflammation is known to be risk factors for metabolic diseases. The purpose of this study was to develop a Food-based Index of Dietary Inflammatory Potential (FBDI) and conduct its validation assessment. This study analyzed raw data from Korean Genome and Epidemiology Study 2012–2014 data of 17,771 people. We carried out the correlation analysis between 51 food groups and hs-CRP. The FBDI was developed by multiple regression method with hs-CRP and selected 17 food group. For the validation of FBDI, 7795 people in the 6th Korea National Health and Nutrition Examination Survey (KNHAES) was used. Binary logistic regression analysis was used for risk analysis of metabolic syndrome and FBDI. The FBDI model included that 7 were composed of anti-inflammatory food groups and 3 of inflammatory food groups. The FBDI was calculated by multiplying the intake of food group by β coefficients. KNHAES were included in the validation of FBDI. The risk of metabolic syndrome was found to be 2.152 times higher in the group with the highest FBDI than in the group with the lowest one (95% Cl:1.458–3.178, p for trend = 0.000). This study developed FBDI reflecting food intake for Koreans, which showed a significant relationship with the risk of metabolic syndrome.

Drug functionalization through formation of hydrophilic groups is the norm in phase I metabolism of drugs for modification of drug action. The reactions involved are mainly oxidative catalyzed mostly by CYP isoenzymes. The benzene ring, as phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e. the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e. the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retaining, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues have been presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design and drug development.

The sustainable metabolic engineering (SME) concept was defined by Stalidzans and Dace as an approach for the selection of most sustainable metabolic engineering designs taking the economic, environmental and social components of sustainability into account. In the centre of sustainability calculations is a genome scale metabolic model that provides full balance of all incoming and outgoing metabolic fluxes at steady state. Therefore, sustainability indicators are assigned for each exchange reaction enabling calculation of sustainability features of consumption or production of each metabolite. The further development of the SME concept depends on its implementation at the computational level to acquire applicable results – sustainable production strain designs. This study proposes for the first time a workflow and tools of SME implementation using constraint based stoichiometric modelling, genome scale metabolic models and growth coupled product synthesis approach. For SME application demonstration purposes, a relatively simple engineering task has been carried out. The most sustainable designs have been identified using Escherichia coli as chassis organism, glucose as a substrate and gene deletions as metabolic engineering tool. A growth coupled production design tool has been used to reduce the variability of sustainability. The 10 000 most sustainable designs were producing succinate as the main product with the number of deleted genes ranging from two to ten. A big number of similar designs has been identified due to the combinatorial explosion of different alternative combinations of gene deletion sets that result in interruption of the same metabolic pathways with the same impact on the metabolism.

Iron overnutrition has been implicated with higher risk of developing metabolic and cardiovascular diseases, including metabolic syndrome (MetS), while iron deficiency anemia exacerbates many underlying chronic conditions. Hemoglobin (Hb) concentration in the blood, which reflects a major functional iron (i.e., heme iron) in the body, may serve as a surrogate of iron nutrition status. We conducted sex-specific observational association studies where we carefully titrated the association between Hb deciles and MetS and its components among the Taiwanese Han Chinese (HC) from the Taiwan Biobank and Europeans of White ancestry from the UK Biobank, representing two large ethnicities. Our data show that at higher-than-normal levels of Hb, increasing deciles of Hb concentration were significantly associated with MetS across all sex subgroups in both ethnicities, with the highest deciles resulting in up to three times greater risks than the reference group [Taiwanese HC: OR=3.17 (95% CI, 2.75-3.67) for Hb >16.5 g/dL in men, OR=3.11 (2.78-3.47) for Hb >14.5 g/dL in women; European Whites: OR=1.89 (1.80-1.98) for Hb >16.24 g/dL in men, OR=2.35 (2.24-2.47) for Hb >14.68 g/dL in women]. The association between stronger risks and increasing Hb deciles was similarly observed with all metabolic components except diabetes. Here we found that both the highest Hb decile groups and contrarily the lowest ones, with respect to the reference, were associated with higher odds of diabetes in both ethnic groups [e.g., Taiwanese HC men: OR=1.64 (1.33-2.02) for Hb >16.5 g/dL, OR=1.71 (1.39-2.10) for Hb <13.5 g/dL; European Whites women: OR=1.39 (1.26-1.45) for Hb >14.68 g/dL, OR=1.81 (1.63-2.01) for Hb <12.39 g/dL]. These findings confirm that elevated Hb concentrations, a potential indicator of iron overnutrition, may play a role in the pathophysiology of MetS and metabolic components.

Metastasis is a systemic condition and the major challenge among cancer types, as it can lead to multiorgan vulnerability. Recently, attention has been drawn to cellular senescence, a complex stress response condition, as a factor implicated in metastatic dissemination and outgrowth. Here, we examine the current knowledge of the features required for cells to invade and colonize secondary organs and how senescent cells can contribute to this process. First, we described the role of senescence in placentation, itself an invasive process which has been linked to higher rates of invasive cancers. Second, we describe how senescent cells can contribute to metastatic dissemination and colonization. Third, we discuss several metabolic adaptations by which senescent cells could promote cancer survival along the metastatic journey. In conclusion, we posit that targeting cellular senescence may have a potential therapeutic efficacy to limit metastasis formation.

(1) Background: Metabolic syndrome is associated with cardiovascular complications. Therefore, this study aims to establish cut points for the conicity index based on the components of the metabolic syndrome and to associate it with characteristics sociodemographic, food consumption and occupational factors in Brazilian rural workers; (2) Methods: Cross-sectional study carried out with farmers. The receiver operating characteristic curve was calculated and the cutoff points for the conicity index were identified by the area under the curve, sensitivity and specificity. The variables included in the binary logistic regression analysis were selected by considering p &lt; 0.20 in the bivariate test; (3) Results: The cut points were similar in females according to both criteria, resulting in a single cut-off of 1.269. In males, the cut points showed differences, resulting in 1.272 according to the NCEP-ATP III and 1.252 according to the IDF. We have shown that younger people, those who work more than 40 hours a week and the lowest contribution of culinary ingredients are associated with increased odds of abdominal obesity. While the consumption of the products they sell or produce decreases these chances; (4) Conclusions: The conicity index showed high discriminatory power for the identification of abdominal obesity in rural workers.

Background: Metabolic syndrome (MS) is associated with a greater risk of morbimortality. Ob-jective: To estimate the prevalence of Metabolic Syndrome (MS) and associated factors in patients of a Psychosocial Care Center (CAPS) in the city of Salvador, state of Bahia, Brazil. Method: Cross-sectional study set at CAPS in the city of Salvador-Bahia, between August 2019 and February 2020. MS was evaluated according to the National Cholesterol Education Program's Adult Treatment Panel III. In addition to descriptive statistics, gross and adjusted prevalence ratios were described. Results: MS was found in 100 (35.2%) individuals, 116 (40.9%) were obese and 165 (58.1%) had increased waist circumference. Polypharmacy was identified in 63 (22.3%) patients and 243 (85.9%) used antipsychotics. In the gross evaluation, the female (PR = 1.88; 95% CI: 1.35-2.63) and the use of antidepressants (PR = 1.41; 95%CI: 1.05-1.88) were associated with MS. After logistic re-gression, depression (PR = 1.86; 95%CI: 1.38-2.51), acanthosis (PR = 1.50; 95%CI: 1.18 - 1.90), use of antipsychotics (PR = 1.88; 95%CI: 1.13 - 2.75) and the hypertriglyceremic waist (PR = 3.33; 95%CI: 2.48- 4.46) were associated with MS. Conclusion: The prevalence of MS alerts to multimorbidity among individuals with mental disorders and the need for clinical screening.

Metabolic flexibility is the ability of an organism to adapt its energy source based on nutrient availability and energy requirements. In humans, this ability has been linked to cardio-metabolic health and healthy aging. Genome-scale metabolic models have been employed to simulate metabolic flexibility by computing the Respiratory Quotient (RQ), which is defined as the ratio of carbon dioxide produced to oxygen consumed, and varies between values of 0.7 for pure fat metabolism and 1.0 for pure carbohydrate metabolism. While the nutritional determinants of metabolic flexibility are known, the role of low energy expenditure and sedentary behavior in the development of metabolic inflexibility is less studied. In this study we present a new description of metabolic flexibility in genome-scale metabolic models which accounts for energy expenditure, and we study the interactions between physical activity and nutrition in a set of patient-derived models of skeletal muscle metabolism in older adults. The simulations show that fuel choice is sensitive to ATP consumption rate in all models tested. The ability to adapt fuel utilization to energy demands is an intrinsic property of the metabolic network

Depression and metabolic diseases often coexist having several features in common, e.g., chronic low-grade inflammation and intestinal dysbiosis. Different microbiota interventions have been proposed to be used as a treatment for these disorders. In the paper we review the efficacy of probiotics in depressive disorders, obesity, metabolic syndrome and its liver equivalent based on the published experimental studies, clinical trials and meta-analyses. Probiotics seem to be effective in reducing depressive symptoms when administered in addition to antidepressants. Additionally, probiotics intake may ameliorate some of the clinical components of metabolic diseases. However, standardized methodology regarding probiotics clinical trials has not been established yet. In this narrative review we discuss current knowledge on the recently used methodology with its strengths and limitations and propose criteria that may be implemented to create a new study of the effectiveness of probiotics in depressive disorders comorbid with metabolic abnormalities. We put across our choice on type of study population, probiotics genus, strains, dosages and formulations, intervention period, as well as primary and secondary outcome measures.

The expression "metabolic reprogramming" is more and more encountered in the literature since the mid-1990s. It seems to encompass several notions depending on the author, but the lack of a clear definition allows it to be used as a "catch-all" expression. With the increased interest in metabolism, and more specifically, in the Warburg effect in cancer research, it seems appropriate to discuss this expression and related concepts in detail.

Euglenids are a group of algae of great interest for biotechnology, with a large and complex metabolic capability. To study the metabolic network, it is necessary to know the subcellular locations of the component enzymes, but despite a long history of research into Euglena, the subcellular locations of many major pathways are only poorly defined. Euglena is phylogenetically distant from other commonly studied algae, they have secondary plastids bounded by three membranes, and they can survive after destruction of their plastids. These unusual features make it difficult to assume that the subcellular organization of the metabolic network will be equivalent to that of other photosynthetic organisms. Moreover, we show here that the presence of the secondary chloroplast means that it is not possible to make reliable predictions of the subcellular locations of enzymes in Euglena using existing informatics tools. In order to generate a model of the central metabolic pathway operating in Euglena we analysed biochemical and proteomic information from a variety of sources to assess the subcellular location of relevant enzymes. We use these assignments to propose the compartmentation of the core metabolic pathways in Euglena, a prerequisite for the further study of the metabolic network of Euglena. This model of the metabolic network shows that, other than photosynthesis, all major pathways present in the chloroplast are duplicated elsewhere in the cell, and that several biosynthetic pathways confined to plastids in higher plants are localized elsewhere in Euglena. Our model demonstrates how this organism can synthesise all the metabolites required for growth from simple carbon inputs, and can survive in the absence of chloroplasts.

Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free fatty acids. It is debated whether the endoplasmic reticulum (ER) stress in monocytic cells can contribute to amplify metabolic inflammation; if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 monocytic cells by treatments with lipopolysaccharide (LPS), palmitic acid (PA), or oleic acid (OA), in the presence or absence of ER stressor thapsigargin (TG). Gene expression of tumor necrosis factor (TNF)-α and markers of ER/oxidative stress was determined by qRT-PCR, TNF-α protein by ELISA, ROS by DCFH-DA assay, HIF-1α/p38/ERK-1,2/NF-κB phosphorylation by immunoblotting, and insulin sensitivity by glucose-uptake assay. Regarding clinical analyses, adipose TNF-α was assessed by qRT-PCR/IHC and plasma TNF-α/hs-CRP/MDA/OX-LDL by ELISA. We found that the cooperative interaction between metabolic and ER stresses promoted TNF-α, ROS, CHOP, ATF6, SOD2, and NRF2 expression (P≤0.0183),. However, glucose uptake was not impaired. TNF-α amplification was dependent on HIF-1α/p38/NF-κB phosphorylation, while MAPK/NF-κB inhibitors and antioxidants/ROS scavengers attenuated TNF-α production (P≤0.05). Individuals with obesity displayed increased adipose TNF-α gene/protein expression as well as elevated plasma levels of TNF-α, CRP, MDA, and OX-LDL (P≤0.05). Our findings support a cooperative interaction between metabolic and ER stresses, favoring inflammation by triggering TNF-α production via the ROS/CHOP/HIF-1α and MAPK/NF-κB dependent mechanisms. This study also shows the therapeutic potential of ROS scavengers/anti-oxidants in inflammatory conditions involving metabolic/ER stresses.

Maternal obesity and gestational diabetes predispose to metabolic disturbances in the next generation. Moreover, the lactation phase also stands as critical for metabolic programming. Nevertheless, the precise mechanisms originating these changes remain unclear. Here we investigate the consequences of maternal diet lipid-rich diet during gestation and lactation, and its impact on metabolism and behavior in the offspring. Two experimental groups of Wistar female rats were used: a control group (NC) that fed a standard diet during gestation and lactation periods and an overnutrition group that fed a high-fat diet (HF, 60% lipid-rich) during the same phases. Offspring were analyzed at postnatal days 21, 28, and 2 months-old (PD21, PD28, PD60) for metabolic profile (weight, fasting glycemia insulin sensitivity, glucose tolerance) and euthanized for brain collection to evaluate by western blot markers of synaptic dynamics, metabolism and inflammation in the hypothalamus, hippocampus and prefrontal cortex. At 2 months-old, behavioral tests for anxiety, stress, cognition, and food habits were conducted. We observe that female offspring born from HF mothers exhibited increased weight gain and decreased glucose tolerance that attenuates with age. In offspring males, weight gain increased at P21 and worsened with age, while glucose tolerance remained unchanged. Offspring of HF mothers exhibited elevated levels of anxiety and stress during behavioral tests, displaying decreased predisposition for curiosity compared to the NC group. In addition, offspring from mothers with HF showed increased food consumption and a lower tendency towards food-related aggression. We conclude that exposure to HF diet during pregnancy and lactation induces dysmetabolism in the offspring accompanied by heightened stress and anxiety. There was sexual dimorphism in metabolic traits but not behavioral phenotypes.

In conclusion, the present study demonstrated the safety of practicing WFM at different TOD. Furthermore, it appears that practicing WF in the evening is safer, as indicated by HRR60s, [Gl], and MBP findings. The utilization of digital biomarkers for monitoring health status during WFM has been shown to be efficient.

This study assessed the associations between host genetic variants and subgingival microbiota in patients with metabolic syndrome (MetS); 103 patients with MetS underwent medical and periodontal examinations and had blood and subgingival plaque samples taken. DNA was extracted and processed (assessing a panel of selected single nucleotide polymorphisms (SNPs) first (hypothesis-testing), and then expanding to a discovery phase. The subgingival plaque microbiome from these patients was profiled. Analysis of associations between host genetic and microbial factors was performed, stratified for periodontal diagnosis. Specific SNPs within RUNX2, CAMTA1 and VDR genes were associated with diversity metrics, with no genome-wide associations detected for periodontitis severity or Mets components at p&lt;10-7. Severe periodontitis was associated with pathogenetic genera and species. Some SNPs correlated with specific bacterial genera, as well as with microbial taxa, notably VDR (rs12717991) with Streptococcus mutans and RUNX2 (rs3749863) with Porphyromonas gingivalis. This is the first study exploring the role of host genotype variation in subgingival microbial dysbiosis in patients with MetS and periodontitis. In conclusion, variation in host genotypes may play a role in the dysregulated immune responses characterizing periodontitis and thus the oral microbiome, suggesting that systemic health-associated host traits further interact with oral health and microbiome.

The purpose of this study was to examine the impact of fructose consumption during the peri-pubertal period on the later onset of metabolic syndrome in rats. Additionally, the study sought to explore the potential of moderate-intensity physical training as a non-pharmacological approach to mitigate the fructose effects. Male rats, 30 days old, received 10% fructose, and were submitted to concomitant moderate-intensity training until 60 days old. They were divided into 4 groups: sedentary control (SC), sedentary fructose (SF), trained control (TC), and trained fructose (TF). Fructose consumption mainly affected adult animals, resulting in glucose intolerance, increased periepididymal fat, and increased total cholesterol, triglycerides, and insulin levels. Furthermore, these rats exhibited reduced sympathetic nerve activity. The moderate running led to a decrease in periepididymal and retroperitoneal adipose tissue, as well as a reduction in total cholesterol and improved glucose tolerance. Peri-pubertal rats that received combination treatments exhibited lower levels of glucose and insulin during an intraperitoneal glucose tolerance test. The results indicate that 10% fructose supplementation during peripuberty predisposes to metabolic syndrome in adulthood. However, simultaneous moderate-intensity exercise training attenuates these effects and induces positive changes in glycemic homeostasis, lipid metabolism, and autonomic nervous system activity.

The aim of this study was to determine the association of metabolic syndrome (MetS) with kidney cancer and the impact of age and gender on such association. Using Korean National Health Insurance Service database, 9,932,670 subjects who had check-up in 2009 were followed up until the diagnosis of kidney cancer or death or until 2019. Kidney cancer was significantly associated with MetS (HR 1.56). This association was higher in the younger age group (HR: 1.82, 1.5, and 1.37 in 20-39 years, 40-64 years, and ≥65 years, respectively). In terms of the association of kidney cancer with obesity and central obesity, young-aged males showed higher HR for kidney cancer than old-aged ones (HR of obesity: 1.96, 1.52, and 1.25; HR of central obesity: 1.94, 1.53, and 1.3 in 20-39 years, 40-64 years, ≥65 years, respectively), while young-aged females showed lower HR. Kidney cancer was associated with obesity and MetS. The association was higher in younger aged population than in older ones. Regarding gender, MetS, obesity, and central obesity showed higher associations with kidney cancer in younger aged male population, while there was no significant difference in such association according to age in females.

The metabolic syndrome, first introduced by Hermann Haller in 1975, was sometimes also known as insulin resistance syndrome, syndrome X, and plurimetabolic syndrome. In 1989 it was rechristened by Kaplan as "Deadly Quartet" based on a consolidation of central obesity, impaired glucose tolerance, dyslipidemia, and systemic hypertension. Metabolic syndrome is positively associated with a pro-inflammatory and pro-thrombotic state, attributed to increased pro-thrombotic and inflammatory markers activity. Moreover, Metabolic syndrome is frequently associated with increased atherosclerotic cardiovascular disease, impaired glucose tolerance, hyperuricemia, obstructive sleep apnea, and chronic kidney disease. Despite concerted endeavors worldwide, the complexity of the pathophysiology of metabolic syndrome is still not clearly understood. Currently, therapeutic possibilities are confined to individual therapy of hyperglycemia, hypertension, hypertriglyceridemia, hyperuricemia, regular physical exercise, and a restricted diet.

One of the most interesting groups of fatty acid derivates is the group of conjugated fatty acids, from which the most researched are conjugated linoleic acid (CLA) and conjugated linolenic acid (CLNA), which are associated with countless health benefits. Sex pheromone mixture of some insect species, including tobacco horn-worm (Manduca sexta), are typical for the production of uncommon C16 long conjugated fatty acids with two and three conjugated double bonds, as opposed to C18 long CLA and CLNA. In this study, M. sexta desaturases MsexD2 and MsexD3 were expressed in multiple strains of Y. lipolytica with different genotypes. Experiments with supplementation of fatty acid methyl esters into the medium resulted in production of novel fatty acids. Using GCxGC-MS 20 new fatty acids with two or three double bonds were identified. Fatty acids with conjugated or isolated double bonds or combination of both were produced in trace amounts. Results of this study prove that Y. lipolytica is capable of synthesizing C16 conjugated fatty acids. Further genetic optimization of the Y. lipolytica genome and optimization of the fermentation process could lead to increased production of novel fatty acid derivatives with biotechnologically interesting properties.

Genome-scale metabolic models (GEMs) play an important role in the phenotype prediction of microorganisms, and their accuracy can be further improved by integrating other types of biological data such as enzyme concentrations and kinetic coefficients. Enzyme-constrained models (ecModels) have been constructed for several species and were successfully applied to increase the production of commodity chemicals. However, there was still no genome-scale ecModel for the important model organism Bacillus subtilis prior to this study. Here, we integrated enzyme kinetic and proteomic data to construct the first genome-scale ecModel of B. subtilis (ecBSU1) using the ECMpy workflow. We first used ecBSU1 to simulate overflow metabolism and explore the trade-off between biomass yield and enzyme usage efficiency. Then, we simulated the growth rate on eight previously published substrates and found that the simulation results of ecBSU1 were in good agreement with the literature. Finally, we identified target genes that enhance the yield of commodity chemicals using ecBSU1, most of which were consistent with the experimental data, and some of which may be potential novel targets for metabolic engineering. This work demonstrates that the integration of enzymatic constraints is an effective method to improve the performance of GEMs. The ecModel can predict overflow metabolism more precisely and can be used for the identification of target genes to guide the rational design of microbial cell factories.

Genome-scale metabolic model (GEM) is a powerful tool for interpreting and predicting cellular phenotypes under various environmental and genetic perturbations. However, GEM only consid-ers stoichiometric constraints, and the simulated growth and product yield values will show a monotonic linear increase with increasing substrate uptake rate, which deviates from the experi-mentally measured values. Recently, the integration of enzymatic constraints into stoichiometry-based GEMs was proven to be effective in making novel discoveries and predicting new engineer-ing targets. Here we present the first genome-scale enzyme-constrained model (eciCW773) for Corynebacterium glutamicum reconstructed by integrating enzyme kinetic data from various sources using ECMpy workflow based on the high-quality GEM of C. glutamicum (obtained by modifying the iCW773 model). The enzyme-constrained model improved the prediction of pheno-types and simulated overflow metabolism, while also recapitulating the trade-off between biomass yield and enzyme usage efficiency. Finally, we used eciCW773 to identify several gene modifica-tion targets for L-lysine production, most of which agree with previously reported genes. This study shows that incorporating enzyme kinetic information into the GEM enhances the cellular phenotypes prediction of C. glutamicum, which can help identify key enzymes and thus provide reliable guidance for metabolic engineering.

Background: A comparison of the amino acid (AA) plasma profile and markers of intestinal absorption-inflammation between healthy subjects aged 65-70 years and age-matched patients affected by stage 3b-4 chronic kidney disease (CKD3b-4) was performed. Methods: eleven healthy volunteers were compared with 12 CKD3b-4 patients at their first outpatient control (T0) and after 12-months (T12). Adherence to a low protein diet (LPD, 0.6±0.1 g/kg/day) was assessed by Urea Nitrogen Appearance. The following parameters were assessed: renal function, nutritional parameters, bioelectrical impedance analysis, plasma levels of 20 total aminoacids (TAAs), both essential (EAAs) including branched-chain amino acids (BCAAs) and non-essential (NEAAs). Zonulin and faecal Calprotectin markers were used to evaluate intestinal permeability/inflammation. Results: Four patients dropped out of the study; in the remaining 8 residual kidney function (RKF) remained stable, their LPD adherence had risen to 0.89g/kg/day, anaemia had worsened and extracellular body fluid had increased. In comparison to healthy subjects, TAA levels of histidine, arginine, asparagine, threonine, glycine, and glutamine had all increased. No variation in BCAAs was observed. A significant increase was detected in faecal calprotectin and zonulin levels in CKD patients as the disease progressed. Conclusions: This study confirms the finding in aged patients of an alteration in levels of several AAs secondary to uraemia. Intestinal markers provide confirmation of a relevant alteration to the intestinal function in CKD patients.

Flaxseed (Linum usitatissinum L.) oil is an important source of α-linolenic (C18:3 ω-3), this polyunsaturated fatty acid is well known for its nutritional role in human and animal diet. Understanding storage lipid biosynthesis in developing flaxseed embryos can lead to an increase in seed yield. While a tremendous amount of work has been done on different plant species to highlight their metabolism during embryos development, flaxseed metabolic flux analysis is still lacking. In this context, we have developed an in vitro cultured developing embryos of flaxseed and determined net fluxes by performing three complementary parallel labeling experiments with 13C-labeled glucose and glutamine. Metabolic fluxes were estimated by computer- aided modeling of the central metabolic network including 11 cofactors of 118 reactions of the central metabolism, 12 pseudo fluxes. A focus on lipid storage biosynthesis and the associated pathways was done in comparison with rapeseed, arabidopsis, maize and sunflower embryos. In our conditions, glucose was the main source of carbone of flaxseed embryos, leading to the conversion of phosphoenolpyruvate to pyruvate. The oxidative pentose phosphate pathway (OPPP) was identified as the producer of NADPH for fatty acid biosynthesis. Overall, the use of 13C-metabolic flux analysis provided new insight into flaxseed embryos metabolic processes involved in storage lipids biosynthesis. The elucidation of the metabolic network of this important crop plant reinforces the relevance of the application of this technique to the analysis of complex plant metabolic systems.

Introduction and objectives: a close association between metabolic syndrome among subjects with erectile dysfunction has been addressed, since mechanisms underlying metabolic syndrome compromise the blood flow to the penis in numerous ways. This study aims to analyze the relationship between erectile dysfunction and metabolic syndrome in a group of Mexican patients, to study the influence of other morbidity factors on erectile dysfunction, and to define the specific metabolic syndrome components most associated with erectile dysfunction severity. Methods: a descriptive and cross-sectional study was completed in a group of 86 adult Mexican patients with previous diagnosis of erectile dysfunction. Participants were classified as with or without metabolic syndrome. Erectile dysfunction severity, alcohol or tobacco consumption, and depressive behavior were identified through validated questionnaires and compared between both groups, as well as anthropometric, biochemical, and clinical parameters. Results: anthropometric measures, laboratory values, clinical characteristics and the Beck Depression Inventory score were significantly different among both groups. Additionally, more patients affected by severe and moderate erectile dysfunction were identified in the group with metabolic syndrome. Among the metabolic syndrome components, HbA1c >5.7% and fasting glucose >110 mg/dl were significantly associated to the development of erectile dysfunction (p = 0.004 and 0.04, respectively). Conclusions: metabolic syndrome components aggravate erectile dysfunction, particularly the lack of glycemic control manifested by Hb1Ac >5.7% and/or fasting glucose >110 mg/dL. The inclusion of fasting glucose and HbA1c as a complementary biochemical screening among patients with erectile dysfunction should be assessed.

Insulin resistance is a prominent pathophysiologic syndrome in a plethora of metabolic disorders including obesity, prediabetes, type 2 Diabetes Mellitus (Ten et al., 2007), impaired glucose tolerance, dyslipidemia, polycystic ovary syndrome and hypercoagulability (Smith & LeRoith, 2004). It is strongly associated with obstructive sleep apnea, hypoventilation syndrome, pancreatitis, nonalcoholic fatty liver disease, steatohepatitis, cirrhosis, gall bladder disease, multiple cancers (breasts, uterus, cervix prostate, kidney, colon, esophagus, pancreas and liver), stroke, cataracts, coronary heart disease, and hypertension. It is also associated with causation of abnormal menses, infertility, polycystic ovary syndrome, osteoarthritis, phlebitis and other venous diseases. Insulin resistance is thought to be caused by intrinsic and extrinsic factors that contribute to its development. Once present, insulin resistance affects the metabolism, behavior, physical appearance and has lasting effects. This paper will review the latest evidence in development of insulin resistance, its pathogenesis and manifestation and its relation to other conditions. The final aim is to raise awareness of its role on diet, metabolic, genetics and microbiome.

Cancer cells are adept at reprogramming energy metabolism and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino acid metabolism, fatty acid oxidation, citric acid cycle, androgen and estrogen metabolism and ROS detoxification distinguished these four groups. Additionally, we developed a workflow to identify potential drugs that can selectively target genes associated with the reactions of interest. MG-132 (a proteasome inhibitor) and OSU-03012 (a celecoxib derivative) were the top-ranking drugs identified from our analysis and known to have anti-tumor activity. Our approach has the potential to provide mechanistic insights into cancer-specific metabolic dependencies, ultimately enabling the identification of potential drug targets for each patient independently, contributing to a rational personalized medicine approach.

The use of recombinant bovine somatotropin (rbST) leads to an increase, in variable amounts, of milk production in buffalo, but there is a lack of information on the influence of rbST on their metabolism. This study looked at the effects of a single 500 mg dose of rbST on lipid profile, liver and kidney function and physical, chemical and cellular constitution of milk in 14 buffalo over 14 days, from the 100th day of lactation, and compared them with 14 animals in a control group. From the 1st day after rbST, there was a rise in beta hydroxybutyrate (β-HBO), possibly due to the higher dry matter intake or by biotransformation of NEFA into β-HBO. Treatment did not influence blood glucose, non-esterified fatty acids (NEFA), triglycerides, cholesterol, total protein, albumin, AST, GGT, bilirubin, urea or creatinine. In 71.3% of the buffalo there was a gradual increase in milk production with maximal response in the first week that was then followed by a gradual decrease, whilst in 21.4%, the increase in production occurred between 7 and 10 days, and only 7.1% of animals did not respond. On the 3rd, 5th, 7th and 10th days after treatment, an increase was found in milk production between the two groups equal to 1.04, 1.52, 1.42 and 1.06 liters, respectively. In relative terms this means an increase in milk production, respectively, of 15.1%; 21.0%; 19.8 % and 15.1 %. The constitution of the milk showed no difference in the amounts of fat, lactose, total solids or somatic cell count; however, on the 3rd day after rbST, there was a decrease in protein; notably, from the 5th day, protein values show no statistical difference. It can be concluded that the application of rbST in buffalo from the 100th day of lactation is metabolically safe, since the treatment neither caused imbalances in fat metabolism nor overloaded the liver or renal function, and the changes in milk composition were transient and limited to a decrease in milk protein.

In recent years, the emergence of the concept of immunometabolism has shed light on the pivotal role that cellular metabolism plays in both the activation of immune cells and the development of immune programs. The antiviral response, a widely distributed defense mechanism used by infected cells, serves to not only control infections but also to attenuates their deleterious effects. The exploration of the role of metabolism in orchestrating the antiviral response represents a burgeoning area of research, especially considering the escalating incidence of viral outbreaks coupled with the increasing prevalence of metabolic diseases. Here, we present a review of current knowledge regarding immunometabolism and the antiviral response during viral infections. Initially, we delve into the concept of immunometabolism by examining its application in the field of cancer—a domain that has long spearheaded inquiries into this fascinating intersection of disciplines. Subsequently, we explore examples of immune cells whose activation is intricately regulated by metabolic processes. Progressing with a systematic and cellular approach, our aim is to unravel the potential role of metabolism in antiviral defense, placing significant emphasis on the innate and canonical interferon response.

Several factors, such as internal algorithm, sensor technology, and obsolescence might skew outcomes when comparing different gas analysers measurements during CPET. Besides aerosol borne infectious disease are a source of contamination during cardiopulmonary exercise tests (CPET). Thus, the main aim of this study was to determine the agreement degree between the Quark RMR and the Jaeger Oxycon Pro, using an antibacterial filter with the latter. Forty-two participants (19-54 years old) performed two non-consecutive maximal graded exercise tests on a cycle-ergometer on two counterbalance and different days using the Oxycon Pro and the Quark RMR in a randomized order. Differences between devices were tested using a generalized linear model adjusted by Bonferroni, and correlation and agreement was assessed using Pearson’s correlation coefficient (R), intraclass coefficient correlation (ICC), Lin’s concordance correlation coefficient (CCC) and Bland-Altman plots. No significant differences were found between devices in any of metabolic or ventilatory parameters for cardiorespiratory fitness assessment (VO_2max: 3131.3±882.1 vs. 3189.8±894.8, p=0.071, VCO_2max: 3436.3±936.0 vs. 3550.3±1043.2, p=0.071, for Quark RMR and Oxycon Pro, respectively). However, Bland-Altman plots showed a trivial tendency towards Oxycon Pro overestimation relative to Quark RMR as air flow volume increases. Both devices showed strong correlation and high level of agreement during maximal and submaximal exercise intensities (Pearson’s R: 0.974 & 0.977; ICC: 0.985 & 0.987; Lin’s CCC: 0.971 & 0.974, for VO₂ and VCO₂, respectively). Therefore, providing consistency to CPET data comparison between both devices, and insight into whether the use of these metabolic carts could be interchangeable or combined when a single device cannot be used for CPET assessment.

Aim: Evaluation of role of supplementation of omega-3 polyunsaturated fatty acids on endothelial function in patients with metabolic syndrome. Methods: Total of 80 patients with metabolic syndrome were enrolled to two groups. We evaluated endothelial function in subjects before and after three-month treatment with omega-3 polyunsaturated fatty acids in dose 2.4g daily (800mg 3 times a day) vs placebo. Using the Endo-PAT2000 device (Itamar Medical Ltd. Caesarea, Israel), reactive hyperemia index – a parameter of endothelial function and augmentation index– a parameter of arterial stiffness were measured. Plasmatic level of glutation peroxidase, homocysteine, apolipoprotein B and lipoprotein (a) were also evaluated. Results: The average values of reactive hyperemia index before the treatment with n-3PUFA was 1.62 ± 0.42 , whereas 1.96 ± 0.62 at the end of the study (p<0.005). Augmentation index changed from 14.66 ± 19.55 to 9.21 ± 15.64 after the treatment (p=0.003). We also observed statistically significant decrease of apolipopotein B (0.94 ± 0.36 vs 1.13 ± 0.35, p = 0.001) and homocysteine (19.31 ± 5.29 vs. 13.78 ± 3.05, p = 0.001) and increase of the glutathion perxidase plasma levels (41.65 ± 8.90 vs. 45.20 ± 8.01), p=0.001. Conclusion: We have observed significant improvement of the endothelial function in subjects with metabolic syndrome treated with omega-3 polyunsaturated fatty acids in dose 2.4g daily.

The number of published studies on curcuminoids in cancer research, including its lead molecule curcumin and synthetic analogs, has been increasing substantially during the past two decades. Insights on the diversity of inhibitory effects they produced on a multitude of pathways involved in carcinogenesis and tumor progression were provided. As this wealth of data was obtained in a setting of various experimental and clinical data, this review first aimed at presenting a chronology of discoveries and an update on their complex in vivo effects. Secondly, there are many interesting questions linked to their pleiotropic effects. One of them, which is a growing research topic, relates to their ability to modulate metabolic reprogramming. This review will also cover the use of curcuminoids as chemosensitizing molecules, that can be combined with several anticancer drugs for reversing the phenomenon of multidrug resistance. Finally, current investigations in these three complementary research fields raise several important questions that will be put in the prospects for the future research related to the importance of these molecules in cancer research.

The sustainable development goals(SDG) of the UNO would be difficult to achieve without prevention of metabolic diseases and other non-communicable diseases (NCDs). Western diet and lifestyle, which are major risk factors of NCDs, are known to cause oxidative stress and decrease in production of molecular hydrogen in the intestines which leads to a decline in endogenous antioxidant status in the body, leading to increase in systemic inflammation. Many experts consider molecular hydrogen as a potential nutrient, which may be administered as gas in the body. There are gaps in the knowledge about the role molecular hydrogen plays, in the treatment of metabolic diseases and other NCDs This review aims to discuss the role of hydrogen in the pathogenesis and prevention of NCDs. Molecular hydrogen (H2) has been studied extensively as a therapeutic gas, with an estimated 2000 publications to date, exploring its potential therapeutic use in 170 disease models across every organ in the mammalian body. Hydrogen therapy can be administered through several methods, such as H2 inhalation, dissolving H2 gas in water to make hydrogen-rich water (HRW) for oral consumption or topical application, or hydrogen-rich saline. The exact mechanism of action of molecular hydrogen is not known but it is in itself a potential antioxidant that can also inhibit hydroxyl and nitrosyl radicals in the cells and tissues. Hydrogen is known to cause a marked decline in oxidative stress, and inflammation that are crucial in the pathogenesis of NCDs. Hydrogen therapy has been found protective against NCDs, including, metabolic diseases, cardiovascular diseases (CVDs), neurodegenerative diseases, chronic kidney disease, cancer and chronic lung diseases.

Hexokinases (HKs) convert hexose sugars to hexose-6-phosphate, thus trapping them inside cells to meet the synthetic and energetic demands. HKs participate in various standard and altered physiological processes, including cancer, primarily through the reprogramming of cellular metabolism. Four canonical HKs have been identified with different expression patterns across tissues. HKs 1-3 play a role in glucose utilization, whereas HK 4 (glucokinase, GCK) also acts as a glucose sensor. Recently, a novel 5^th HK, hexokinase domain containing 1 (HKDC1), has been identified, which plays a role in whole-body glucose utilization and insulin sensitivity. Beyond the metabolic functions, HKDC1 is differentially expressed in many forms of human cancer. This review focuses on the role of HKs, particularly HKDC1, in metabolic reprogramming and cancer progression.

Gout is not only associated with obstructive sleep apnea (OSA), but the intermittent episodes of hypoxia that occur with OSA may also have a role in causing gout. Epidemiological studies have documented a higher incidence and prevalence of gout in individuals diagnosed with OSA than in individuals never diagnosed with OSA. The pathophysiology of OSA’s chronic episodes of hypoxia leading to hyperuricemia and gout involves boththe overproduction and underexcretion of uric acid. Treating OSA may be an additional way to control gout and its life-threatening comorbidities. Clinicians are urged to evaluate their patients with hyperuricemia/gout for OSA as it may lead to alternative ways to control gout with superior outcomes that simply pharmacologic treatment alone.

Cells produce reactive oxygen species (ROS) as by-products of metabolism, which can give rise to a two-sided effect on the body under balanced and imbalanced oxidant homeostasis conditions. Antioxidant supplements exert their beneficial efficacy in the treatment of metabolic diseases only when the oxidant homeostasis is imbalanced with the over-production of ROS. Over-supplementation of antioxidant(s) can also cause an imbalanced oxidant homeostasis to exert detriments to the induction of metabolic diseases. This commentary raises a concern that prior to precise supplementation of antioxidants, an establishment of oxidant homeostasis status is required in avoiding an imbalanced oxidant homeostasis in vivo. In searching for valid oxidant stress makers, 3-Nitrotyrosine seems to fit in with the selection criteria and its quantification can be correlated with the degree of oxidative stress in vivo.

Two putative boar pheromones (Androstenone and Androstenol) were discovered in endangered mouse deer during captive breeding program. This study further examined the molecular characteristics, pheromone synthesis pathway, and the functional role of these pheromones in reproduction of mouse deer. CYP17A1 and CYB5 genes were cloned and expressed in HEK-293, COS-7 cell lines and gonads of mouse deer to investigate CYP17A1 gene’s andien-β-synthase activity towards synthesis of sex pheromones in mouse deer. An enzyme immunoassay was also developed and standardized to measure the fecal androstenone during reproductive cycles of mouse deer. Results showed that mouse deer’s CYP17A1 gene possesses andien-β-synthase activity and could transform pregnenolone into 5,16-androstadien-3β-ol. The expression of CYP17A1 gene upregulated in the testis and ovary, compared to other tissues in mouse deer. Significantly elevated pheromones and estrogens were recorded prior to delivery and postpartum estrus / mating in mouse deer. Further, there were weak correlations between fecal pheromones and estrogens/ androgens in mouse deer during breeding season. The findings suggest that the boar pheromones might play a direct role in the reproductive activities of mouse deer which might be used for breeding of mouse deer elsewhere.

When exposed to a viral infection, the attacked cells promptly set up defence mechanisms. Part of antiviral responses, the innate immune interferon pathway and associated interferon stimulated genes are notably allowing the production of proteins bearing an antiviral activity. Numerous viruses are able to evade the interferon response, highlighting the importance of controlling this pathway to ensure their efficient replication. Several viruses are also known to manipulate the metabolism of infected cells to optimize the availability of amino acids, nucleotides and lipids. They then benefit from a reprogramming of the metabolism that favours glycolysis instead of mitochondrial respiration. Given the increasingly discussed crosstalk between metabolism and innate immunity, we wondered whether this switch from glycolysis to mitochondrial respiration would be beneficial or deleterious for an efficient antiviral response. We used a cell based model of metabolic reprogramming. Interestingly, we showed that increased mitochondrial respiration was associated with an enhanced interferon response following poly:IC stimulation. This suggests that during viral infection, the metabolic reprogramming towards glycolysis is also part of the virus' strategies to inhibit the antiviral response.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n=55; approximately 800-1000 IU from combined sources) or monitored therapy (n=54; with an option of dose modification). 25(OH)D concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52±2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (&gt;90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p=0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

: Increased glucose and choline uptake are hallmarks of cancer. We investigated if the uptake and conversion of [2H9]choline alone and together with that of [6,6’ 2H2]glucose can be assessed in subcutaneous tumors by deuterium metabolic imaging (DMI) after bolus administration of these compounds. Therefore tumors with human renal carcinoma cells were grown subcutaneously in mice up to ~0.5 cm3. Mice were anesthetized with isoflurane and IV infused in the MR magnet for ~20 sec with ~0.2 ml solutions containing either [2H9]choline (0.05g/kg) alone or together with [6,6’ 2H2]glucose (1.3g/kg). 2H MR was performed on a 11.7T MR system with a home-built 2H/1H coil using a 900 excitation pulse and 400ms repetition time. 3D DMI was recorded at high resolution (2x2x2mm) in 37 min or at low resolution (3.7x3.7x3.7mm) in 2:24 min. Absolute tissue concentrations were calculate assuming initial [HOD]=13.7mM. Within 5 minutes after [2H9]choline infusion its signal appeared in tumor spectra representing concentration increasing up to 0.3–1.2 mM and then slowly decreased or remained constant over 100 minutes. In plasma [2H9]choline disappeared within 15 minutes post-infusion implying that its tumor signal arises from tissue and not blood. After infusing a mixture of [2H9]choline and [6,6’ 2H2]glucose their signals were observed separately in tumor 2H spectra. Over time the [2H9]choline signal broadened, possibly due to conversion to other choline compounds, [[6,6’ 2H2]glucose] declined, [HOD] increased and a lactate signal appeared, reflecting glycolysis. Metabolic maps of all 2H compounds were reconstructed from high resolution DMIs. As choline infusion and glucose DMI is feasible in patients, their simultaneous detection has clinical potential for tumor characterization.

There is a huge need to search for new treatment options and potential biomarkers of therapeutic response to antidepressant treatment. Depression and metabolic syndrome often coexist while pathophysiological overlap, including microbiota changes, may play a role. The aim of the study is to assess the effect of probiotic supplementation on symptoms of depression, anxiety and stress, metabolic parameters, inflammation and oxidative stress markers, and faecal microbiota in adult patients with depressive disorders depending on the co-occurance of MetS. The trial will be a four-arm, parallel group, prospective, randomized, double-blind, controlled design that will include 200 participants and will last 20 weeks. The probiotic preparation will contain Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175. We will assess the level of depression, anxiety and stress, quality of life, blood pressure, body mass index and waist circumference, white blood cells count, serum levels of C-reactive protein, HDL cholesterol, triglicerides, fasting glucose, faecal microbiota composition and the level of some faecal microbiota metabolites, as well as inflammation markers and oxidative stress parameters in serum. The trial may establish a safe and easy-to-use treatment option as an adjunct in a subpopulation of depressive patients only partially responsive to pharmacologic treatment. (ClinicalTrials.gov identifier: ).

Ustilago maydis, member of the Ustilaginaceae family, is a promising host for the production of several metabolites including itaconic acid. This dicarboxylate has great potential as a bio-based building block in the polymer industry, and is of special interest for pharmaceutical applications. Several itaconate overproducing Ustilago strains have been generated by metabolic and morphology engineering. This yielded stabilized unicellular morphology through fuz7 deletion, reduction of by-product formation through deletion of genes responsible for itaconate oxidation and (glyco)lipid production, and the overexpression of the regulator of the itaconate cluster ria1 and the mitochondrial tricarboxylate transporter encoded by mttA from Aspergillus terreus. In this study, itaconate production was further optimized by consolidating these different optimizations into one strain. The combined modifications resulted in itaconic acid production at theoretical maximal yield, which was achieved under biotechnologically relevant fed-batch fermentations with continuous feed.

Signaling through GPR109a, the putative receptor for the endogenous ligand β-OH butyrate, inhibits adipose tissue lipolysis. Niacin, an anti-atherosclerotic drug that can induce insulin resistance, activates GPR109a at nM concentrations. GPR109a is not essential for niacin to improve serum lipid profiles. To better understand the involvement of GPR109a signaling in regulating glucose and lipid metabolism, we treated GPR109a wildtype (+/+) and knockout (-/-) mice with repeated overnight injections of saline or niacin in physiological states characterized by low (ad libitum fed) or high (16h fasted) concentrations of the endogenous ligand, β-OH butyrate. In the fed state, niacin increased expression of PEPCK mRNA independent of genotype, while increasing CPT1 mRNA only in GPR109a -/- mice. Niacin decreased fasting serum non-esterified fatty acid concentrations in both GPR109a +/+ and -/- mice. Independent of GPR109a expression, niacin blunted fast-induced hepatic triglyceride accumulation and peroxisome proliferator activated receptor α (PPARα) mRNA expression. Surprisingly, GPR109a knockout did not affect glucose or lipid homeostasis or hepatic gene expression in either fed or fasted mice. In turn, GPR109a does not appear to be essential for the metabolic response to the ketogenic state or the pharmacological benefits associated with niacin.

The national rate of obesity in US Hispanic/Latinos exceeds all other major ethnic subgroups and represents an important health disparity. Plant-based diet interventions that emphasize whole plant foods with minimal processing and less refined grains and sugar have shown have shown great promise in control of obesity, but there is a paucity of data translating this treatment effect to disparity populations. The objective of our study was to evaluate the efficacy and scalability of the Healthy Eating Lifestyle Program (HELP) – a hospital-based, family centered, culturally tailored, plant-based diet intervention for Hispanic/Latino pediatric obesity patients and their families. Our evaluation methods included: 1) a quasi-experimental, one group, longitudinal study to measures changes in BMI at 0, 6, and 18 weeks of follow-up, and 2) A stakeholder analysis consisting of six key informant interviews of HELP program staff. We found a significant decrease in body mass index across all adults (-0.2 kg/m² p=0.0047), that was much stronger in men. For children ages 5-12 years, there was also a significant decrease in BMI Z score from pre- to post- intervention (p=0.04). Program strengths were the cultural tailoring of the plant-based diet choices, and allowing a tiered approached that did not require adherence to strict vegetarianism. Our pilot study findings from HELP raise the possibility that incorporating plant-based diet choices into the treatment of pediatric obesity patients and their families can be an effective addition to a culturally responsive care model.

The prevalence and factors associated with metabolic syndrome (MetS) remain unknown in Malaysian vegetarians. This cross-sectional study aimed to determine the prevalence of MetS among vegetarians in Kuala Lumpur and Selangor and its associated factors. The data on socio-demographic characteristics, vegetarianism practices, lifestyle behaviours, body weight, height, waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and blood lipid profiles were collected from 273 vegetarians. A majority of the respondents were lacto-ovo vegetarians (44.0%), females (64.8%) and Chinese (54.9%). The prevalence of MetS was 24.2%. High BP (48.7%) and high WC (43.6%) were the most common MetS components. Females had lower WC, SBP, DBP, FBG, TG and higher HDL-c (p < 0.05) as compared to males. Multiple logistic regression analysis showed that advancing in age (OR = 1.03, 95% CI: 1.00-1.06), and overweight and obesity (OR = 7.90, 95% CI: 4.13-15.11) were the risk factors of MetS after adjusted for sex. This study found that one in four vegetarians had MetS. The present findings emphasize the need to focus among vegetarians with older age. An intervention program to reduce BMI should be established among vegetarians, especially among those vegetarians who were overweight and obese.

To date, several independent methods and algorithms exist exploiting constraint-based stoichiometric models to find metabolic engineering strategies that optimize microbial production performance. Optimization procedures based on metaheuristics facilitate a straightforward adaption and expansion of engineering objectives as well as fitness functions, while being particularly suited for solving problems of high complexity. With the increasing interest in multi-scale models and a need for solving advanced engineering problems, we strive to advance genetic algorithms, which stand out due to their intuitive optimization principles and proven usefulness in this field of research. A drawback of genetic algorithms is that premature convergence to sub-optimal solutions easily occurs if the optimization parameters are not adapted to the specific problem. Here, we conducted comprehensive parameter sensitivity analyses to study their impact on finding optimal strain designs. We further demonstrate the capability of genetic algorithms to simultaneously handle (i) multiple, non-linear engineering objectives, (ii) the identification of gene target-sets according to logical gene-protein-reaction associations, (iii) minimization of the number of network perturbations, and (iv) the insertion of non-native reactions, while employing genome-scale metabolic models. This framework adds a level of sophistication in terms of strain design robustness, which is exemplarily tested on succinate overproduction in Escherichia coli.

The dietary pattern that characterizes the Western diet is strongly associated with obesity and related metabolic diseases, but biological mechanisms supporting these associations remain largely unknown. We argue that the Western diet promotes inflammation that arises from both structural and behavioral changes in the resident microbiome. The environment created in the gut by ultra-processed foods, a hallmark of the Western diet, is an evolutionarily unique selection ground for microbes that can promote diverse forms of inflammatory disease. Recognizing the importance of the microbiome in the development of diet-related disease has implications for future research, public dietary advice as well as food production practices. Research into food patterns suggests that whole foods are a common denominator of diets associated with a low level of diet-related disease. Hence, by studying how ultra-processing changes the properties of whole foods and how these foods affect the gut microbiome, more useful dietary guidelines can be made. Innovations in food production should be focusing on enabling health in the super-organism of man and microbe, and stronger regulation of potentially hazardous components of food products is warranted.

Autophagy is a highly conserved catabolic mechanism that mediates the degradation of damaged cellular components by inducing their fusion with lysosomes. This process provides cells with an alternative source of energy for the synthesis of new proteins and the maintenance of metabolic homeostasis in stressful environments. Numerous studies have demonstrated beneficial roles for the induction as well as the suppression of autophagy in cancer cells. Autophagy may induce either survival or death depending on the cell/tissue type. Radiation therapy is widely used therapeutic option to treat cancer, and it induces autophagy in human cancer cell line. Also, melatonin seems to affect cancer cell death via regulation of programmed cell death. In this review, we summarize the current understanding of autophagy and its regulation in cancer.

Gait variability (GV) is a crucial measure of inconsistency of muscular activities or body seg-mental movements during repeated tasks. Hence, GV might serve as a relevant and sensitive measure to quantify adjustments of walking control. However, has not been clarified whether GV is associated with walking speed to exploit effective better coordination level. Fourteen male stu-dents (age 22.4 ± 2.7 years, body mass 74.9 ± 6.8 kg, body height 1.78 ± 0.05 m) took part in this study. After three days of walking 1 km each day at a self-selected speed (SS) on asphalt with Apple Watch S. 7 (AppleTM), the participants were randomly evaluated on a treadmill at three different walking speed intensities for 10 minutes each one, at SS-20% / SS+20% of SS, with 5 minutes of passive recovery in-between. Heart rate (HR) was monitored beat-to beat and nor-malized as HR%MAX, while the rate of perceived exertion (RPE) (CR-10) was asked after each trial. Kinematic analysis was performed assessing the Contact Time (CT), Swing Time (ST), Stride Length (SL), Stride Cycle (SC) and Gait Variability as Phase Coordination Index (PCI). RPE and HR increased with higher walking speed (P = 0.005 and P = 0.035, respectively). CT and SC decreased as the speed increased (P = 0.0001 and P = 0.013, respectively), while ST remained un-changed (P = 0.277). SL increased with higher walking speed (P = 0.0001). Conversely, PCI was 3.81 ± 0.88 % (high variability) at 3.96 ± 0.47 km·h-1, 2.64 ± 0.75 % (low variability) at SS (4.94 ± 0.58 km·h-1), 3.36 ± 1.09 % (high variability) at 5.94 ± 0.70 km·h-1 (P = 0.001). These results indi-cate that while the metabolic demand and kinematics variables changing linearly with increasing speed, the most effective GV was observed at SS. Therefore, SS could be a new methodological approach to choose the individual walking speed, normalize the speed intensity, and avoid a gait pattern alteration.

Studies investigating the acute effect of postprandial exercise (PPE) on glucose responses exhibit significant heterogeneity in terms of participant demographic, exercise protocol, and exercise timing post-meal. As such, this study aimed to further analyze the existing literature on the impact of PPE on glycemic control in individuals with overweight, obesity, and type 2 diabetes (T2D). Literature search was conducted through databases including PubMed, CINAHL, and Google Scholar. Thirty-one original research studies that met the inclusion criteria were selected. The random-effect meta-analysis was performed to compare postprandial glucose area under the curve (AUC) and 24-h mean glucose levels between PPE and the time-matched no-exercise control (CON). Subgroup analysis was conducted to explore whether the glucose-lowering effect of PPE could be influenced by exercise duration, exercise timing post-meal, and disease status of participants. This study revealed significantly reduced glucose AUC (Hedges’ g = -0.317; SE = 0.057; p < 0.05) and 24-hour mean glucose levels (Hedges’ g = -0.328; SE = 0.062; p < 0.05) following PPE than CON. The reduction in glucose AUC was greater (p < 0.05) following PPE lasting >30 min than ≤30 min. The reduction in 24-hour mean glucose levels was also greater (p < 0.05) following PPE initiated ≥60 min than <60 min post-meal and in those with T2D than those without T2D. PPE offers a viable approach for glucose management and can be performed in various forms so long as exercise duration is sufficient. The glucose-lowering effect of PPE may be further enhanced by initiating it after the first hour post-meal. PPE represents a promising strategy, particularly for patients with T2D.

The aim was to determine the effect of Sechium edule var. nigrum spinosum (chayote) on gene ex-pression related to antioxidant protection mechanisms and the inflammatory process in older adults with metabolic syndrome (MetS). A quasi-experimental study was carried out in a con-venience sample of 46 older adults diagnosed with MetS: (i) placebo group (PG; n=20), (ii) ex-perimental group (EG; n=26). Clinical, biochemical, and anthropometric parameters, SOD, GPx, and CAT enzyme activity, total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), cytokines (IL-6, IL-8 and TNF-α) and mRNA expression of (SOD, GPx, CAT, IL-6, IL-8, TNF-α, Nrf2, NFkB p50 and NFkB p65), were measured at baseline and 6 months post-intervention. A statistically significant decrease was observed in TOS (baseline, 28.9 ± 3.6 vs. post, 23.7 ± 3.4, p < 0.01) and OSI (baseline, 24.1 ± 3.8 vs. post, 17.7 ± 4). As well as the increase in IL-6 (baseline, 10.7 ± 1.1 vs. post, 12.3 ± 2, p = 0.03), SOD activity (baseline, 167.1 ± 11.9 vs. post, 180.6 ± 7.6, p < 0.05), CAT activity (baseline, 1.0 ± 0.2 vs. post, 1.3 ± 0.2, p < 0.01) and TAS (baseline, 1.1 ± 0.1 vs. post, 1.4 ± 0.1, p < 0.01) in the EG compared to the PG. Regarding the expression of Nrf2, SOD and IL-6, the EG showed a significant increase vs basal levels (47%, 44% and 43%, re-spectively). Our findings suggest that Sechium edule supplementation promotes the antioxidant response and decreases oxidative stress via Nrf2.

Metabolic-associated fatty liver disease (MAFLD) and diabetic kidney disease (DKD) share various pathophysiological factors, and epidemiological evidence suggests that these two diseases are associated. Albuminuria and the estimated glomerular filtration rate, which are conventional biomarkers of DKD, are reportedly associated with the risk or severity of MAFLD. Recently, novel DKD biomarkers reflecting renal tubular injury have been introduced to complement conventional DKD markers. In this article, we looked at previous studies that showed an association between MAFLD and DKD and also reviewed the significance of DKD biomarkers as predictive risk factors for MAFLD.

Endocrine and nervous systems reciprocally interact to manage physiological individual functions and homeostasis. The nervous system modulates hormone release through the hypothalamus, the main cerebrally specialized structure of the neuroendocrine system. Indeed, it is involved in various metabolic processes, administering hormone and neuropeptide release at different levels. This complex activity is affected by neurons of various cerebral areas, environmental factors, peripheral organs, and mediators through feedback mechanisms. Therefore, neuroendocrine pathways have a key role in metabolic homeostasis control, and their abnormalities have been associated with the development of Metabolic Syndrome (MetS) in children. The impaired functioning of genes, hormones, and neuropeptides of various neuroendocrine pathways involved in several metabolic processes has been related to an increased risk of dyslipidaemia, visceral obesity, insulin resistance, type 2 diabetes mellitus, and hypertension. This review examines the neuroendocrine effects on the risk of MetS in children, identifying and underlying the several conditions associated with neuroendocrine pathway disruption. Neuroendocrine systems should be considered in the complex pathophysiology of MetS, and, when genetic or epigenetic mutations in "hot" pathways occur, they could be studied for new potential target therapies in severe and drug-resistant paediatric forms of MetS.

Information about molecular mechanism of pesticide resistance in the rust-red flour beetle, a major pest destroying grains and flour across Nigeria is grossly lacking, hindering evidence-based con-trol. Here, we identified to species level three populations of the red-flour beetle from Kano, Ni-geria, as Tribolium castaneum, and investigated the mechanism driving their insecticide resistance. IRAC susceptibility bioassays established high cypermethrin resistance, with LC50s of 4.35-5.46mg/ml in the three populations, NNFM, R/Zaki and Yankaba. High DDT and malathion resistance was observed in NNFM, with LC50s of 15.32- and 3.71mg/ml, respectively. High sus-ceptibility was observed towards dichlorvos in all three populations with LC50s of 0.17-0.35mg/ml, respectively. Synergist bioassay with piperonylbutoxide significantly restored cypermethrin sus-ceptibility, with mortality increasing almost threefold, from 24.8% obtained from 1.25mg/ml of cypermethrin, to 63.3% in synergised group (p=0.013), suggesting a preeminent role of P450s. The two major knockdown resistance (kdr) mutations, T929I and L1014F in the IIS4 and IIS6 fragments of voltage-gated sodium channel were not detected in both cypermethrin-alive and cyperme-thrin-dead beetles, suggesting lesser role of target-site insensitivity. These findings highlight the need to explore alternative control tools for this pest and/or explore incorporation of synergists, like piperonylbutoxide as additional chemistries into pesticides formulations to improve their ef-ficacy.

This review aimed at synthesizing the mechanisms and outcomes of metabolic surgery on hormones, adipokines, metabolomics, and at the molecular level. We reviewed the endocrine, microRNA, and metabolomics changes in human and animal models following metabolic surgery for the treatment of obesity and diabetes. PubMed, Science Direct, Scopus, and Google Scholar databases were searched up to February 2022. The most relevant studies in the area over the past 17 years have been considered for this review. In most cases, metabolic procedures especially those that include intestinal bypass components, showed remission of type 2 diabetes. This involves a variety of weight-independent mechanisms to improve glucose homeostasis, improving insulin sensitivity, and secretion. The miRNAs’ dysregulated expressions have essential roles in metabolic processes. Metabolic surgery is a potentially sustainable treatment that can modify a patient’s physiology and glucose regulation mechanism. The feasibility and role of miRNA are important for potential targeted genetic pathways in future obesity with type 2 diabetes management.

SGLT2 inhibitors act to induce glucosuria and have been shown to be efficacious in the treatment of type II diabetes mellitus but have also been shown to positively affect cardiovascular conditions and some benefitting kidney function. SGLT2i have shown to be effective in more advanced conditions but may eventually be a treatment in more general metabolic dysfunction. Metabolic syndrome is a clinical diagnosis for establishing risk for ischemic heart disease and diabetes. The prevalence of type II diabetes mellitus, heart disease, and severe vascular events steadily increased over recent decades. In addition to the established benefits of diet and exercise, SGLT2 inhibitor therapy may be able to aid in the treatment of metabolic syndrome from its proven cardiovascular and anti-hyperglycemic benefits. Pharmacologic modeling in canines is also considered, as they present with similar diagnoses and offer a model that shares many of the characteristics of humans in metabolic dysfunction.

Background: There has been evidence that metabolic syndrome (MetS) may increase the risk of frailty. However, there is limited evidence on this association in Asian populations. Aims: This study aims to identify the association between MetS and frailty in older people in Vietnam. Methods: This is a cross-sectional analysis of a dataset obtained from an observational study on frailty and sarcopenia in patients aged ≥60 at a geriatric hospital in Vietnam. Frailty was defined by the frailty phenotype. Participants were defined as having MetS if they had ≥3 out of 5 criteria from the definition of the National Cholesterol Education Program (NCEP) Adults Treatment Panel (ATP) III. Multiple logistic regression models were performed to estimate the risk of having frailty in patients with MetS. Results: There were 669 participants (mean age 71, 60.2% female), 62.3% had MetS and 39.0% was frail. The prevalence of frailty was 42.2% in participants with MetS, 33.7% in participants without MetS (p=0.029). On logistic regression models, MetS was associated with increased likelihood of being frail (adjusted OR 1.52, 95%CI 1.01-2.28), allowing for age, sex, education, nutritional status, history of hospitalisation and chronic diseases. Conclusion: There was a significant association between MetS and frailty in this population. Further longitudinal studies are required to confirm this association.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

1) Background: Fetal Growth Restriction (FGR) has been associated with adverse perinatal outcomes and epigenetic modifications that impact gene expression leading to permanent changes of fetal metabolic pathways and thereby influence development of disease in childhood and adult life. Both clinical and experimental studies showed that maternal nutrition during pregnancy is critical since malnutrition adversely affects fetal growth and physiology. In this study, we investigated the result of maternal food restriction on liver protein expression in Wistar male newborn pups. (2) Materials & methods: Pups born to food restricted mothers were subdivided to FGR and non-FGR groups. Livers of control, FGR and non-FGR groups were analyzed using quantitative proteomics. (3) Results: In total 6665 proteins were profiled. Of these, 451 and 751 were differentially expressed in FGR and non-FGR vs. control respectively, whereas 229 were common between the two groups. Bioinformatics analysis of the differentially expressed proteins (DEPs) in FGR vs. control revealed: induction of the super-pathway of cholesterol biosynthesis and inhibition of thyroid hormone metabolism, fatty acid beta oxidation and apelin liver signaling pathway. In the DEPs of non-FGR vs. control groups there was inhibition of thyroid hormone metabolism, fatty acid beta oxidation and apelin liver signaling pathway as well. (4) Conclusion: This study demonstrates the impact of prenatal food restriction on the proteomic liver profile of FGR and non-FGR offspring underlying the importance of both prenatal adversities and birth weight on liver dependent postnatal disease.

Metabolite transport across cellular membranes is a key feature of living organisms. Specialized proteins or protein complexes mediate such transport processes and are accessible to genetic engineering approaches. This special issue will reflect on the different transport between cellular compartments. It will provide an overview about different transporter classes and metabolic engineering approaches in different organisms ranging from Bacteria to Eukarya. The transport mechanisms energetics of these compounds were thought little of, and most consideration was given to the designing of metabolic pathways. Gram-negative microbes discharge a wide scope of proteins whose capacities incorporate biogenesis of organelles, for example, pilli and flagella, supplement securing, destructiveness, and efflux of medications and different poisons. Six particular emission frameworks have been appeared to intervene protein send out through the inward and external layers of Gram-negative microbes. These pathways are exceptionally monitored all through the Gram-negative bacterial species. In Gram-positive microscopic organisms, discharged proteins are usually moved across the single layer by the Sec pathway or the two-arginine (Tat) pathway. Recently efforts focused on transporter and metabolite engineering, visualize the improvement and enhancement of microbial cell to pass such metabolites these metabolite carrier proteins are inserted into the inner membrane of mitochondria across the inner membrane, specialized carrier proteins are necessary that mediate the transport into and out of the mitochondrial matrix. Two main strategies for metabolic engineering in plants: the introduction of genes encoding new enzymes and the use of TFs controlling specialized metabolic pathways

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.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Purpose: To investigate the alterations in nitro-oxidative stress (OS) and antioxidant status in adolescents with metabolic syndrome (MetS) and whether these alterations occur independently from effects of overweight or obesity.Methods: Blood was collected in 47 adolescents with MetS and 94 adolescents without MetS as assessed with the International Diabetes Federation criteria. The International Obesity Task Force (IOTF) criteria were used to classify the subjects into those with overweight or obesity. We measured nitro-oxidative biomarkers including nitric oxide metabolites (NOx), lipid hydroperoxides (LOOH), and malondialdehyde (MDA), and antioxidant biomarkers, i.e. total radical-trapping antioxidant parameter (TRAP), paraoxonase (PON)-1 activity, thiol (SH-) groups, as well as tumor necrosis factor-α, glucose, insulin, triglycerides, uric acid and high-density lipoprotein cholesterol (HDL-C).Results: Logistic regression analysis showed that increased MDA and NOx and a lowered TRAP/uric acid ratio were associated with MetS. Machine learning including soft independent modeling of class analogy (SIMCA) showed that the top-3 most important features of MetS were increased glucose and MDA and lowered HDL-C. Support vector machine using MDA, glucose, insulin, HDL-C, triglycerides and body mass index as input variables yielded a 10-fold cross-validated accuracy of 89.8% when discriminating MetS from controls. The association between MetS and increased MDA was independent from the effects of overweight-obesity. glucose, insulin, triglycerides and HDL-C.Conclusion: In adolescents, increased MDA formation is a key component of MetS, indicating that increased production of reactive oxygen species with consequent lipid peroxidation and aldehyde formation participate in the development of MetS.

Monitoring glycosylation changes within cells upon response to stimuli remains challenging because of the complexity of this large family of post-translational modifications (PTMs). We have developed an original tool enabling labeling and visualization of the cell cycle key-regulator b-catenin in its O-GlcNAcylated form based on intramolecular Förster resonance energy transfer (FRET) technology in cells. We opted for a bioorthogonal chemical reporter strategy based on the dual-labeling of b-catenin with a green fluorescent protein (GFP) for protein sequence combined with a chemically-clicked imaging probe for PTM resulting in a fast and easy to monitor qualitative FRET assay. We validated this technology by imaging the O-GlcNAcylation status of b-catenin in HeLa cells. Moreover, the changes in O-GlcNAcylation of b-catenin were varied by perturbing global cellular O-GlcNAc levels with inhibitors of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Finally, we provided a flowchart demonstrating how this technology is transposable to any kind of glycosylation.

High fat-diet (HFD) feeding is known to induce metabolic dysregulation, however less is known on its impact in promoting the hypercoagulable state. The current study aimed to evaluate platelet-monocyte aggregate (PMA) formation following short-term HFD feeding. This is particularly important for understanding the link between inflammation and the hypercoagulable state during the early onset of metabolic dysregulation. To explore such a hypothesis, mice were fed a HFD for 8 weeks, with body weights as well as insulin and blood glucose levels monitored on weekly basis during this period. Basal hematological measurements were determined and the levels of spontaneous peripheral blood PMAs were assessed using whole blood flow cytometry. The results showed that although there were no significant differences in body weights, mice on HFD displayed impaired glucose tolerance and markedly raised insulin levels. These metabolic abnormalities were accompanied by elevated baseline PMA levels as an indication of hypercoagulation. Importantly, it was evident that baseline levels of monocytes, measured using the CD14 monocyte marker were significantly decreased in HFD-fed mice when compared to controls. In summary, the current evidence shows that in addition to causing glucose intolerance, such as that identified in a prediabetic state, HFD-feeding can promote undesirable hypercoagulation, the major consequence implicated in the development of cardiovascular complications.

The ANTIATERO-ALIM study was a randomized, parallel design nutritional trial testing functional food (FF) diets against the usual diet recommended in the metabolic syndrome. Functional meals included balsamic vinegar from apples and honey and grape juice enriched with polyphenols from seeds of red grapes. 300 patients with metabolic syndrome were randomized into 4 groups: gr.1: FF + Ω-3 supplements, gr.2: FF, gr.3: Ω-3 supplements, gr.4: control. IRHOMA insulin resistance, plasma lipids and oxidative stress were assessed at inclusion and at 6 months. After 6 months there was a very significant decrease of oxidative stress in group 3, followed by a significant decrease in groups 1 and 2.

Rice (Oryza sativa L.) processing yields ~60 million metric tons of bran annually. Rice genes producing bran metabolites of nutritional and human health importance were assessed across 17 diverse cultivars from seven countries using non-targeted metabolomics and resulted in 378-430 metabolites. Gambiaka cultivar had the highest number and Njavara had the lowest number of metabolites. The 71 rice bran compounds of significant variation by cultivar included 21 amino acids, seven carbohydrates, two metabolites from cofactors and vitamins, 33 lipids, six nucleotides, and two secondary metabolites. Tryptophan, -ketoglutarate, γ-tocopherol/β-tocopherol and γ-tocotrienol are example bran metabolites with extensive cultivar variation and genetic information. 34 rice bran components that varied between cultivars linked to 535 putative biosynthetic genes using to the OryzaCyc 4.0, Plant Metabolic Network database. Rice genes responsible for bran composition with animal and human health importance is available for rice breeding programs to utilize in crop improvement.

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.

The increasing prevalence of obesity and sedentary lifestyles has led to an increased incidence of metabolic syndrome (MetS) worldwide. In Taiwan, middle-aged women are at a greater risk of MetS, type 2 diabetes, and cardiovascular disease than men are because they have more subcutaneous fat and larger waist circumferences compared to men with equal visceral fat levels. This study investigated the effects of calorie restriction supplemented with fish oil (CRF) in middle-aged women with MetS. For 12 weeks, 75 eligible participants were randomly assigned either calorie restriction (CR) or CRF. Both dietary intervention groups were further divided into two age groups: ≤45 and >45 years. The changes in MetS severity, inflammatory status, iron status, and red blood cell fatty acid profile were evaluated. Seventy-one participants completed the trial. Both dietary interventions significantly ameliorated MetS and improved the participants’ inflammatory status. CR significantly increased total iron binding capacity, whereas CRF increased hepcidin levels. Furthermore, CRF significantly increased the n-6/n-3 and arachidonic acid/docosahexaenoic acid ratios. In conclusion, CR and CRF improved the anthropometric and MetS characteristics of early-middle aged women, including body weight, blood glucose levels, triglyceride levels, as well as the scores for the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity cheque index. Dietary intervention was more effective in >45-year-old women than ≤45-year-old women.

In a 24-week-long experiment, 31 rats were assigned to one of 3groups: a Control group receiving standard chow and water, a Fructose group receiving standard chow and a 20% fructose solution, or an STZ+lipids group that received a fat-enriched diet following a single 25 mg/kg streptozotocin injection at the onset of the diet. The STZ+lipids group exhibited hyperglycemia, hyperketonemia, and a decline in both heart rate and cardiac function. Conversely, there were no significant bio-chemical differences between the Fructose and Control groups. However, the Fructose group experienced a more pronounced decrease in heart function. Respirometric analyses unveiled a substantial increase in mitochondrial respiration across all adipose tissue types in both dietary intervention groups, with greater changes observed in the Fructose group. Correlation analyses demonstrated a positive association between respiratory indices and fat volume, heart function, and tissue blood flow in the Control group. In the STZ+lipids and Fructose groups, respiratory indices exhibited a positive correlation with heart rate and a negative correlation with dietary exposure characteristics. Overall, the markedly elevated mitochondrial respiration rate observed in rats subjected to hypercaloric diets was linked to characteristics indicative of dietary resilience, rather than measures of circulation.

Variation in metabolite profiles of under high salinity and nitrogen constraint conditions are the key issues of study at the present. To investigate the optimum NaCl and NaNO3 concentration and the corresponding metabolic pathways of astaxanthin accumulation in H. pluvialis, a 26-day batch culture experiment of H. pluvialis treated under the variable concentration gradients of NaCl and NaNO₃ were conducted. The results indicated that 7.5g•L^-1 and nitrogen-deficient were the optimum NaCl and NaNO₃ concentration for the astaxanthin accumulation according to single factor experiments respectively, under which the highest contents of astaxanthin accumulated in H. pluvialis reached up to 7.51mg•L^-1 and 5.60mg•L^-1. A total of 132 metabolites were analysed using LC-MS/MS technique, among which 30 differential metabolites with statistical significance were highlighted. Subsequently, 18 and 10 differential metabolic pathways in the high salinity and nitrogen-deficient treatments with statistic significance were enriched and annotated respectively. Furthermore, the metabolic networks related to the astaxanthin accumulation were constucted based on the crucial pathways and metabolites. Moreover, the major carbon metabolism in H. pluvialis under the high salinity and nitrogen deficient stress were presented, which exhibited the characteristics in the identified metabolites changes under the different stress conditions. The results did not only demonstrate the differential metabolic networks and the distinct changes in the metabolites involved in the major carbon metabolism, related to the astaxanthin accumulation in H. pluvialis under the different stress factors, but provided the regulation targets for astaxanthin production in practice.

Metabolic syndrome is a growing global health problem. Evidence suggests that diets rich in phytochemical-containing herbs and spices can contribute to reduced risk of chronic disease. This review assesses the scope of evidence supporting the use of herbs and spices in the diet for prevention or treatment of metabolic syndrome and associated health conditions. A search of PubMed and Scopus databases was carried out to assess the available clinical or cohort evidence for culinary doses of commonly used herbs and spices. Trials that were measuring health factors related to metabolic disorders or the health of individuals with metabolic syndrome or associated diseases were included. Out of a total of 1742 papers identified, there were 146 relevant studies on black pepper, chilli, cardamom, cinnamon, coriander, cumin, fennel, fenugreek, garlic, ginger, Nigella seed, rosemary, sage and turmeric. No relevant research was found for cloves, mint, oregano, parsley or thyme. Cinnamon, fenugreek and ginger were the herbs/spices with the most published trials on them and showed promise for glycaemic control. Cardamom appears to have potential to reduce inflammatory markers, and cinnamon, ginger and turmeric for blood lipids. Patients with type 2 diabetes were the population most likely to be included in studies, but the preventative benefits of herbs/spices in healthy populations were also investigated, particularly for chilli, ginger and cinnamon. There is evidence for the beneficial effect of culinary doses of many common herbs/spices in the prevention and treatment of metabolic syndrome and associated disorders.

Microbial cell factories offer an eco-friendly alternative for transforming raw materials into commercially valuable products, primarily because of their reduced carbon impact compared to conventional industrial procedures. These systems often depend on lignocellulosic materials, mainly pentose and hexose sugars, richly available carbon reservoirs. Nevertheless, these resources might not always be efficient due to the limited supply, significant cost, and other considerable obstacles. One major hurdle when working with sugars derived from lignocellulosic biomass, especially glucose, is balancing carbon allocation to satisfy energy, cofactor, and other essential component needs for cellular proliferation while maintaining a robust yield. Furthermore, nearly half or more of this carbon is inevitably lost as CO2 during the biosynthesis processes, which serves to generate the energy necessary for maintaining cell growth and other regular metabolic activities. This carbon loss lowers the theoretical production yield and compromises the benefit of reducing greenhouse gas emissions – a fundamental advantage of biomanufacturing. This review paper posits the perspectives of using CO2 from atmosphere, industrial wastes, or the exhausted gases generated in microbial fermentation as a feedstock for biomanufacturing. Both one-step direct CO2 fixation or two-step indirect CO2 fixation and conversion strategies are discussed, which can minimize the carbon loss, significantly increase the carbon yield, and eventually achieve the carbon-neutral or -negative goals. The one-step strategy uses novel metabolic pathway design and engineering approaches to directly fix the CO2 via the pathway toward the synthesis of the desired fermentation products. Due to the limitation of the yield and efficiency in one-step CO2 fixation, the two-step strategy aims to completely avoid carbon loss in biomanufacturing by integrating a first electrochemical fixation of the exhausted CO2 into C1/C2 products such as formate, methanol, acetate, and ethanol and a second fermentation unit to utilize the CO2-derived C1/C2 chemicals or co-utilize both C5/C6 sugars and C1/C2 chemicals for product formation. The great potentials and challenges of using CO2 as a feedstock for further biomanufacturing are also discussed.

Metabolic bone diseases cover a broad spectrum of disorders that share alterations of bone metabolism leading to a defective skeleton, associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, being TP53 one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of TP53 is a genetic factor associated with several pathologies, including cancer, stroke and osteoporosis. Here, we aim to analyze the influence of the TP53 Arg72Pro SNP on bone mass in the humanized Tp53 Arg72Pro knock-in mice. This work reported on the influence of TP53 Arg72Pro polymorphism in bone microarchitecture, OPG gene expression and apoptosis bone status. The results showed that the proline variant of TP53 Arg72Pro polymorphism (Pro72-p53) was associated with deteriorated bone tissue, lower OPG/RANK ratio and lower apoptosis in bone tissue. In conclusion, the TP53 Arg72Pro polymorphism modulates bone microarchitecture and may be a genetic biomarker to identify individuals with an increased risk of suffering metabolic bone alterations

The traditional processing of Dendrobium officinale (DO) is manufactured through five necessary processing steps: fresh strips, drying at 85 °C, curling, molding, and drying at 35 °C (Fengdou), and the antioxidant activity of DO were increased after processing into Fengdou. To comprehensively analyses the changing functional components, a plant-wide target metabolomics were employed. In total, 739 differential ingredients were identified in five processing treatments, mainly highlighting differences in variation with phenolic acids, flavonoids, lipids, and amino acids and their derivatives, and glycosylation of aglycone result in the up-regulation in flavonoid glycosides levels. Temperature is a key step in DO processing production. In addition, the main enrichment of specific differential ingredients was found in five different metabolic pathways, including glucosinolate biosynthesis, linoleic acid metabolism, flavonoid biosynthesis, phenylpropanoid biosynthesis, ubiquinone and other terpene quinone biosynthesis. Correlation analysis clarified that total phenols and flavonoids showed a significant positive correlation with antioxidant capacity. This study provides new insights into the influence of processing processes on DO quality, which may lead to guidance for the high-quality production of DO.

Achieving synchronization between the central and peripheral body clocks is essential for ensuring optimal metabolic function. Meal timing is an emerging field of research that investigates the influence of eating patterns on our circadian rhythm, metabolism, and overall health. This narrative review examines the relationship between meal timing, circadian rhythm, clock genes, circadian hormones, and metabolic function. It analyzes existing literature and experimental data to explore the connection between mealtime, circadian rhythms, and metabolic processes. The available evidence highlights the importance of aligning mealtime with the body’s natural rhythms to promote metabolic health and prevent metabolic disorders. Specifically, studies show that consuming meals later in the day is associated with a elevated prevalence of metabolic disorders, while early time-restricted eating, such as having an early breakfast and an earlier dinner, improves levels of glucose in the blood and substrate oxidation. Circadian hormones, including cortisol and melatonin, interact with mealtimes and play vital roles in regulating metabolic processes. Cortisol, aligned with dawn in diurnal mammals, activates energy reserves, stimulates appetite, influences clock gene expression, and synchronizes peripheral clocks. Consuming meals during periods of elevated melatonin levels, specifically during the circadian night, has been correlated with potential implications for glucose tolerance. Understanding the mechanisms of central and peripheral clock synchronization, including genetics, interactions with chronotype, sleep duration, and hormonal changes, provides valuable insights for optimizing dietary strategies and timing. This knowledge contributes to improved overall health and well-being by aligning mealtime with the body’s natural circadian rhythm.

Background and Aims: Metabolic Syndrome (MetS), a global problem, predisposes to an increased risk for Type 2 diabetes and premature cardiovascular disease. While MetS is associated with central obesity, there is scanty data on adipocyte hypertrophy, increased fat cell size (FCS), in MetS. The aim of this study was to investigate FCS status in gluteal adipose tissue biopsy of patients with nascent MetS without the confounding of diabetes, cardiovascular disease, smoking or lipid therapy . Methods and Results: Fasting blood and subcutaneous gluteal adipose tissue (SAT) biopsy were obtained in MetS (n=20) and controls (n=19). Cardio metabolic features, FFA levels, hsCRP and HOMA-IR were significantly increased in patients with MetS. Waist-circumference adjusted-FCS was significantly increased in patients with MetS and increased with increasing severity of MetS. Furthermore, there were significant correlations between FCS with glucose, HDL-C and the ratio of TG: HDL-C. There were significant correlations between FCS and FFA, endotoxin and monocyte TLR4 abundance. Also, FCS correlated with readouts of NLRP3 Inflammasome activity. Most importantly, FCS correlated with markers of fibrosis and angiogenesis. Conclusions: In conclusion, in patients with nascent MetS, we demonstrate WC-adjusted increase in FCS from gluteal AT that correlated with cellular inflammation, fibrosis and angiogenesis. While these preliminary observations were in gluteal fat, future studies are warranted to confirm these findings in visceral and other fat depots.

The pandemic of obesity worldwide has been recognized as a very important challenge. Within its complexity the identification of higher risk patients becomes essential since it seems unsustainable trying to offer access to treatment to all people with obesity. Several new approaches have recently been presented as important tools for risk stratification. This research applied some of these tools in a cross-sectional study involving adults with obesity classes I, II, III and super obesity. The participants had their cardiometabolic risk profile assessed. The study included adults with obesity, aged 18 to 50 years (n=404) who were evaluated for anthropometric, body composition, hemodynamic, physical fitness and biochemical assessments. These variables were used to identify the prevalence of risk factors for cardiometabolic diseases according to the classes of obesity, by gender and age group. The results showed a high prevalence of risk factors, especially among the upper classes of obesity (BMI &gt; 35 kg/m2) using single parameters as the waist circumference with almost 90% above the cut-off point. But there were also smaller numbers as the Glycated Hemoglobin whose prevalence was around 30%. Indexes like the atherogenic index of plasma (AIP) had the highest prevalence, with 100% of the male participants identified with increased risk for cardiovascular diseases.

Alkaloids are the most diversified nitrogen-containing secondary metabolites having antioxi-dant, and antimicrobial properties and are extensively used in pharmaceuticals to treat different types of cancer. Nicotiana serves as a reservoir of anticancer alkaloids and is also used as a model plant for the de novo synthesis of various anti-cancer molecules through genetic engineering. Up to 4% of the total dry weight of Nicotiana was found to be composed of alkaloids where nicotine, nornicotine, anatabine, and anabasine are reported as the dominant alkaloids. And, among the alkaloids present in Nicotiana, β-carboline (Harmane and Norharmane), Kynurenines are found to show anti-tumor effects, especially in the case of colon and breast cancer. Creating new or shunting of existing biosynthesis pathways in different species of Nicotiana resulted in de novo or increased synthesis of different anti-tumor molecules or their derivatives or precursors includ-ing Taxadiane (~22.5 µg/g), Artemisinin (~120 μg/g), Parthenolide (~2.05 ng/g), Costunolide (~60 ng/g), Etoposide (~1 mg/g), Crocin (~400 µg/g), Catharanthine (~60 ng/g), Tabersonine (~10 ng/g), Strictosidine (~0.23 mg/g), etc. Enrich precursor pool especially Dimethylallyl Diphos-phate (DMAPP) and down-regulating of other bi-product pathways, compartmentalization or metabolic shunting, or organelle-specific reconstitution of the precursor pool might trigger the enhanced accumulation of the targeted anticancer alkaloid in Nicotiana.

The antibody Trastuzumab (Tz) targeting ERBB2 has improved the prognosis of patients with breast cancer (BCa) that overexpress this receptor. Resistance to Tz negatively impacts prognosis. Several mechanisms have been reported to cause Tz resistance. The objective of this study was to identify common mechanisms in in vitro models of acquired BCa Tz resistance. In particular, we used three widely available ERBB2+ BCa cell lines adapted to grow in Tz. We performed several analyses to address possible changes in phenotype, proliferation, and ERBB2 membrane expres-sion common to the three Tz-R cell lines compared to wt, but none was found. High-resolution mass spectrometry analysis identified, instead, a common set of differentially expressed proteins (DEPs) in Tz-R vs. wt cells. Furthermore, bioinformatic tools revealed that all three Tz-R cell models shared a modulation of proteins involved in the metabolism of lipids, organophosphate biosynthetic process, and macromolecule methylation. Ultrastructural analysis confirmed altera-tion of lipid droplets in resistant cells. Our data strongly support the hypothesis that complex metabolic adaptation, including lipid metabolism, protein phosphorylation, and possibly chro-matin remodeling, may fuel Tz resistance. The identification of a common set of 10 DEPs in all three TZ-resistant cell lines may provide novel targets for therapeutic intervention.

The frequency of non-alcoholic fatty liver disease (NAFLD) has exacerbated setting diagnostic challenges, which increases the need for reliable non-invasive diagnostic tools. Due to the importance of gut-liver axis in the progression of NAFLD, studies try to reveal microbial signatures in NAFLD, evaluate them as diagnostic biomarkers and to predict the disease progression. The gut microbiome affects human physiology by processing the ingested food to bioactive metabolites. These molecules can penetrate the portal vein and the liver to promote or prevent hepatic fat accumulation. Here findings of human fecal metagenomic and metabolomic studies in relation to NAFLD are reviewed. The studies present mostly distinct and even contradictory findings on microbial metabolites and functional genes in NAFLD. The most reproducing microbial biomarkers are increased lipopolysaccharides and peptidoglycan biosynthesis, enhanced degradation of lysine, increased levels of branched chain amino acids as well as altered lipid and carbohydrate metabolism. Among other causes, the discrepancies between the studies may be related to the obesity status of the patients and severity of NAFLD. In none of the studies except one, diet was considered, though it is an important factor driving the gut microbiota metabolism. The future studies should consider diet in the analyses.

Assessing the genetic diversity of metabolic resistance genes such as cytochrome P450s helps to understand the dynamics and evolution of resistance in the field. Here, we analysed the polymor-phisms of CYP6M2 and CYP6P4 associated with pyrethroid resistance in Anopheles coluzzii and An. gambiae, to detect potential resistance markers. Field-caught resistant mosquitoes and susceptible lab-strains were crossed and F4 was exposed to permethrin for 15min and 90min to discriminate highly susceptible (HS) and highly resistant (HR) mosquitoes respectively. Significant permethrin mortality reduction was observed after pre-exposure to PBO, suggesting P450s genes involvement. QPCR analysis revealed significant over-expression of CYP6M2 (FC=19.57 [95%CI 13.96-25.18] for An. coluzzii; 10.16 [7.86-12.46] for An. gambiae) and CYP6P4 (FC=6.73 [6.15-7.30] An. coluzzii; 23.62 [26.48-20.76] An. gambiae). Full-gene and ≈1kb upstream were sequenced. For CYP6M2, upstream region shows low diversity in HR and HS (overall Hd=0.49, π=0.018), whereas the full-gene shows allelic-variation but without evidence of ongoing selection. CYP6P4 upstream region showed a lower diversity in HR (Hd=0.48) than HS (Hd=0.86) of An. gambiae. These results highlighted that CYP6P4-associated resistance is potentially driven by modification in upstream region. However further work is needed to determine the real causative variants which will help design rapid detec-tion tools.

The prevalence of obesity in Korean adults was 56.1% in 2019. This study aimed to find obesity phenotypes from the KNHANES(2015–2019) and determine the risk factors associated with each type. In 15,179 participants, three obesity phenotypes, high BMI (short heavy obesity, n=1,685), high waist circumference (WC) (tall abdominal obesity, n=549), and BMI/WC combination (heavy abdominal obesity, n=3,538), were compared to non-OB (n=9,425). Marital status, lower income and education levels were highly associated with abdominal obesity. Insufficient exercise or skipping breakfast were associated with the WC or BMI/WC obesity type. The BMI/WC risk was 3.25 times higher in males with high TG and 4.6–4.8 times higher in females with high FAS or TG, and the risk increased to 7-8 times higher in three combinations (HYP+HDLc+FBS) compared to the control. The K-Score to test balanced diets was lower in BMI/WC than in others. Low intakes of FI-4(fruits) in men and FI-2(meat), FI-3 (vegetables), and FI-5 (milk/milk products) in women with BMI/WC and WC types, but BMI type was not associated with diets. Compared to BMI, the BMI/WC or WC obesity type was an indicator of metabolically unhealthy obesity associated with obesogenic environments including food/diets pattern and unhealthy behaviors.

Over the past decade, studies have demonstrated the importance of bioactive metabolites derived from the microbiota in the regulation of physiological processes essential for homeostasis and the maintenance of human health. Strategies to modulate the production of these metabolites in the gastrointestinal tract hold promise for combating dysbiosis or inflammatory bowel disease. Metabolic engineering of probiotics could be one of these solutions. In this work, we engineered Escherichia coli Nissle 1917 (EcN) to overproduce spermidine, a metabolite known for its anti-immunosenescence and anti-inflammatory properties. Using a rational synthetic biology approach coupled with analysis by high resolution mass spectrometry, we designed in several steps and validated engineered probiotics overproducing and excreting spermidine. Based on our results, we first added the enzyme substrate putrescine and showed the overproduction of spermidine and decided to add a transporter limiting the production of the acetylated form of spermidine. Next, we used untargeted metabolomics to study the impact of engineering on the central metabolism of E. coli Nissle. Untargeted metabolomics appears to be a good strategy to optimize the metabolic engineering of probiotic strains and thus accelerate their development for personalized medicine.

Leishmaniasis is a tropical disease caused by a protozoan parasite Leishmania that is transmitted via infected female sandflies. At present, leishmaniasis treatment mainly counts on chemotherapy. The currently available drugs against leishmaniasis are costly, toxic, with multiple side effects, and limitations in the administration route. The rapid emergence of drug resistance has severely reduced the potency of anti-leishmanial drugs. As a result, there is a pressing need for the development of novel anti-leishmanial drugs with high potency, low cost, acceptable toxicity, and good pharmacokinetics features. Due to the availability of preclinical data, drug repurposing is a valuable approach for speeding up the development of effective antileishmanial through pointing to new drug targets in less time having low costs and risk. Metabolic pathways of this parasite play a crucial role in the growth and proliferation of Leishmania species during the various stages of their life cycle. Based on available genomics/proteomics information, known pathways-based (sterol biosynthetic pathway, purine salvage pathway, glycolysis, GPI biosynthesis, hypusine, polyamine biosynthesis) Leishmania-specific proteins could be targeted with known drugs that were used in other diseases, resulting in finding new promising anti-leishmanial therapeutics. The present review discusses various metabolic pathways of the Leishmania parasite and some drug candidates targeting these pathways effectively that could be potent drugs against leishmaniasis in the future.

Pharmaceutically active compounds and organic pollutants are becoming a major environmental dispute possessing serious threat to the water bodies and terrestrial ecosystem. Microorganisms are capable of the self-purification process, and hence the microbial degradation is considered a lucrative method to counteract the therapeutic and recalcitrant pollutants. Pharmaceutical toxicants in aquatic system can be treated by conventional wastewater treatment, but slow sludge settling, presence of mixture of pharmaceuticals and recalcitrant compounds often pose a potential ecological risk. Some microbial strains are very effective in reducing the chemical oxygen demand (COD), biological oxygen demand (BOD), total dissolved solids (TDS), and turbidity in pharmaceutical industrial wastewater treatment. The natural microbial community has a significant role in the ecological processes of pharmaceutical and organic compounds, including non-steroidal anti-inflammatory drugs, analgesics, blood lipid regulators and other micropollutants. Specific bacterial isolates can act as biodegraders, and fungal treatment could offer protection to the ecosystem. These microorganisms use the pollutants as their sole carbon source and transform the contaminants by co-metabolic pathways. Natural attenuation by native microorganisms, biostimulation and bioaugmentation are the processes employed to degrade the target contaminant. Microorganisms may also be genetically engineered to improve the neutralization efficiency, which would assist in the mineralization of the pollutants. Thus, employing microorganisms to detoxify the pollutants probably enhances the sustainable potential biodegradability, improves water quality standards and ensures eco-friendly alternative bioremediation strategy.

Macronutrient intake is important in the prevention and management of Metabolic Syndrome (MetS). We characterized energy and macronutrient intake of Koreans diagnosed with MetS at recruitment of the Health Examinee (HEXA) cohort. We included 130,423 participants aged 40-69 years for analysis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated to evaluate the intake of macronutrient. Low energy (OR= 0.94, 95% CI: 0.89-0.98) and fat intake (OR=0.91, 95% CI: 0.86-0.97) was observed among 50-59 year-old men. Only postmenopausal women had lower intake of total energy (OR= 0.95, 95% CI: 0.92-0.97) while low fat intake was observed in all women (OR= 0.80 95% CI: 0.77-0.83). For carbohydrate intake, the OR were 1.14 (95% CI: 1.08-1.22) and 1.17 (95% CI: 1.08-1.27) among women in their 50’s and 60’s respectively. Protein intake was low (OR=0.90, 95% CI: 0.86-0.95) and (OR=0.88, 95% CI: 0.82-0.94) among women in their 50’s and 60’s respectively. High intake of plant carbohydrates in women (OR=1.16, 95% CI: 1.12-1.20) and plant protein in both genders (OR=1.09, 95% CI: 1.05-1.13) were observed, but low intake of total energy, fat and animal-source carbohydrates in both genders. Fat intake was low regardless of food source. In conclusion, high consumption of plant-source and low consumption of animal-source macronutrients was observed in Korean adult diagnosed MetS.