Gender Differences in Liver Steatosis and Fibrosis in Overweight and Obese Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease before and after 8 Weeks of Very Low-Calorie Ketogenic Diet.

Obesity and metabolic syndrome are linked to steatotic liver disease (SLD), the most common form of chronic liver disease. Lifestyle modifications and dieting are strategies that can prevent metabolic dysfunction-associated steatotic liver disease (MASLD). The very low-calorie ketogenic diet (VLCKD) is a helpful treatment for MASLD and has been recommended for people affected by obesity; we evaluated the effect of gender on steatosis and fibrosis in a cohort of 112 overweight or obese patients undergoing an eight-week treatment with a VLCKD. Differences between the genders in terms of anthropometric measures, body composition, and metabolic indicators were examined before, during, and after the nutritional intervention. At baseline, there were significant differences between men and women in terms of anthropometric parameters, blood pressure, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting insulin, hepatic markers, and lipid profile. Men had considerably higher levels of liver steatosis (measured by CAP) and liver stiffness (measured by E) under basal conditions than women. After the VLCKD, there were reductions in both genders of controlled attenuation parameter (CAP), body weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, insulin resistance, fat mass (FM), free fat mass (FFM), and fasting blood glucose, insulin, glycated hemoglobin (HbA1c), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, alanine transaminase (ALT), gamma-glutamyl transferase (γGT), and uric acid levels. Only in men, liver stiffness, aspartate aminotransferase (AST), creatinine, and C-reactive protein (CRP) levels significantly decreased. Moreover, men had significantly greater levels of liver steatosis: the male gender featured an increase of 23.96 points of the Fibroscan CAP. Men exhibited higher levels of steatosis and fibrosis than women, and these differences persist despite VLCKD. These gender-specific variations in steatosis and fibrosis levels could be caused by hormonal and metabolic factors, suggesting that different therapeutic strategies might be required depending on the gender.

Do Precision and Personalised Nutrition Interventions Improve Risk Factors in Adults with Prediabetes or Metabolic Syndrome? A Systematic Review of Randomised Controlled Trials.

This review aimed to synthesise existing literature on the efficacy of personalised or precision nutrition (PPN) interventions, including medical nutrition therapy (MNT), in improving outcomes related to glycaemic control (HbA1c, post-prandial glucose [PPG], and fasting blood glucose), anthropometry (weight, BMI, and waist circumference [WC]), blood lipids, blood pressure (BP), and dietary intake among adults with prediabetes or metabolic syndrome (MetS). Six databases were systematically searched (Scopus, Medline, Embase, CINAHL, PsycINFO, and Cochrane) for randomised controlled trials (RCTs) published from January 2000 to 16 April 2023. The Academy of Nutrition and Dietetics Quality Criteria were used to assess the risk of bias. Seven RCTs (n = 873), comprising five PPN and two MNT interventions, lasting 3-24 months were included. Consistent and significant improvements favouring PPN and MNT interventions were reported across studies that examined outcomes like HbA1c, PPG, and waist circumference. Results for other measures, including fasting blood glucose, HOMA-IR, blood lipids, BP, and diet, were inconsistent. Longer, more frequent interventions yielded greater improvements, especially for HbA1c and WC. However, more research in studies with larger sample sizes and standardised PPN definitions is needed. Future studies should also investigate combining MNT with contemporary PPN factors, including genetic, epigenetic, metabolomic, and metagenomic data.

Fish oil supplementation in obese rats ameliorates metabolic syndrome response.

Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response.

Effects on cardiovascular risk factors of a low- vs high-glycemic index Mediterranean diet in high cardiometabolic risk individuals: the MEDGI-Carb study.

BACKGROUND: The role of dietary Glycemic Index (GI), independently of fiber intake, in modulating cardiovascular disease (CVD) risk among non-diabetic individuals has not been fully elucidated. OBJECTIVE: To evaluate the effects of a low- versus a high-GI diet, based on a Mediterranean dietary pattern, on cardiometabolic risk factors in individuals at high CVD risk, participating in the MEDGI-Carb intervention study. SUBJECTS AND METHODS: 160 individuals, aged 30-69 years, BMI 25-37 kg/m2, with a waist circumference >102 cm (males) or >88 cm (females) and one feature of the metabolic syndrome, participated in a multi-national (Italy, Sweden, USA) randomized controlled parallel group trial. Participants were assigned to a low GI (< 55) or high-GI MedDiet ( > 70) for 12 weeks. The diets were isoenergetic and similar for available carbohydrate (270 g/d) and fiber (35 g/d) content. Fasting metabolic parameters were evaluated in the whole cohort, while an 8-h triglyceride profile (after standard breakfast and lunch) was evaluated only in the Italian cohort. RESULTS: Blood pressure and most fasting metabolic parameters improved at the end of the dietary intervention (time effect, p < 0.05 for all); however, no differences were observed between the low- and the high-GI MedDiet groups (time x group effect; p > 0.05 for all). Conversely, the low-GI diet, compared with high-GI diet, significantly reduced the 8-h triglyceride profile (p < 0.017, time*group effect) that was measured only in the Italian cohort. However, it induced a reduction of plasma triglycerides after lunch (tAUC) that was of only borderline statistically significance (p = 0.065). CONCLUSIONS: Consuming a low-GI in comparison with a high-GI MedDiet does not differentially affect the major cardiometabolic risk factors at fasting in individuals at increased cardiometabolic risk. Conversely, it could reduce postprandial plasma triglycerides. CLINICAL TRIAL REGISTRY NUMBER: NCT03410719, ( https://clinicaltrials.gov ).

Peanut (Arachis hypogaea L.) seeds and by-products in metabolic syndrome and cardiovascular disorders: A systematic review of clinical studies.

BACKGROUND: Cardiovascular disease (CVDs) is the leading cause of death worldwide. The main risk factors are hypertension, diabetes, obesity, and increased serum lipids. The peanut (Arachis hypogaea L.), also known as the groundnut, goober, pindar, or monkey nut, belongs to the Fabaceae family and is the fourth most cultivated oilseed in the world. The seeds and skin of peanuts possess a rich phytochemical profile composed of antioxidants, such as phenolic acids, stilbenes, flavonoids, and phytosterols. Peanut consumption can provide numerous health benefits, such as anti-obesity, antidiabetic, antihypertensive, and hypolipidemic effects. Accordingly, peanuts have the potential to treat CVD and counteract its risk factors. PURPOSE: This study aims to critically evaluate the effects of peanuts on metabolic syndrome (MetS) and CVD risk factors based on clinical studies. METHOD: This review includes studies indexed in MEDLINE-PubMed, COCHRANE, and EMBASE, and the Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were adhered to. RESULTS: Nineteen studies were included and indicated that the consumption of raw peanuts or differing forms of processed foods containing peanut products and phytochemicals could improve metabolic parameters, such as glycemia, insulinemia, glycated hemoglobin, lipids, body mass index, waist circumference, atherogenic indices, and endothelial function. CONCLUSION: We propose that this legume and its products be used as a sustainable and low-cost alternative for the prevention and treatment of MetS and CVD. However, further research with larger sample sizes, longer intervention durations, and more diverse populations is needed to understand the full benefit of peanut consumption in MetS and CVD.

Effects of coconut oil long-term supplementation in Wistar rats during metabolic syndrome - regulation of metabolic conditions involving glucose homeostasis, inflammatory signals, and oxidative stress.

This study was designed to evaluate the long-term effects of Fructose (20%) feeding in rats, simulating metabolic syndrome (MetS), and the effects of coconut oil (C.O.) supplementation when administered in a MetS context. MetS is a cluster of systemic conditions that represent an increased chance of developing cardiovascular diseases and type 2 diabetes in the future. C.O. has been the target of media speculation, and recent studies report inconsistent results. C.O. improved glucose homeostasis and reduced fat accumulation in Fructose-fed rats while decreasing the levels of triglycerides (TGs) in the liver. C.O. supplementation also increased TGs levels and fructosamine in serum during MetS, possibly due to white adipose tissue breakdown and high fructose feeding. Pro-inflammatory cytokines IL-1ß and TNF-α were also increased in rats treated with Fructose and C.O. Oxidative stress marker nitrotyrosine is increased in fructose-fed animals, and C.O. treatment did not prevent this damage. No significant changes were observed in lipoperoxidation marker 4-Hydroxynonenal; however, fructose feeding increased total conjugated dienes and caused conjugated dienes to switch their conformation from cis-trans to trans-trans, which was not prevented by C.O. treatment. Potential benefits of C.O. have been reported with inconsistent results, and indeed we observed some benefits of C.O. supplementation in aiding weight loss, fat accumulation, and improving glucose homeostasis. Nonetheless, we also demonstrated that long-term C.O. supplementation could present some problematic effects with higher risk for individuals suffering MetS, including increased TGs and fructosamine levels and conformational changes in dienes.

Intermittent fasting and changes in Galectin-3: A secondary analysis of a randomized controlled trial of disease-free subjects.

BACKGROUND AND AIMS: Intermittent fasting reduces risk of interrelated cardiometabolic diseases, including type 2 diabetes and heart failure (HF). Previously, we reported that intermittent fasting reduced homeostasis model assessment of insulin resistance (HOMA-IR) and Metabolic Syndrome Score (MSS) in the WONDERFUL Trial. Galectin-3 may act to reduce insulin resistance. This post hoc evaluation assessed whether intermittent fasting increased galectin-3. METHODS AND RESULTS: The WONDERFUL Trial enrolled adults ages 21-70 years with ≥1 metabolic syndrome features or type 2 diabetes who were not taking anti-diabetic medication, were free of statins, and had elevated LDL-C. Subjects were randomized to water-only 24-h intermittent fasting conducted twice-per-week for 4 weeks and once-per-week for 22 weeks or to a parallel control arm with ad libitum energy intake. The study evaluated 26-week change scores of galectin-3 and other biomarkers. Overall, n = 67 subjects (intermittent fasting: n = 36; control: n = 31) completed the trial and had galectin-3 results. At 26-weeks, the galectin-3 change score was increased by intermittent fasting (median: 0.793 ng/mL, IQR: -0.538, 2.245) versus control (median: -0.332 ng/mL, IQR: -0.992, 0.776; p = 0.021). Galectin-3 changes correlated inversely with 26-week change scores of HOMA-IR (r = -0.288, p = 0.018) and MSS (r = -0.238, p = 0.052). Other HF biomarkers were unchanged by fasting. CONCLUSION: A 24-h water-only intermittent fasting regimen increased galectin-3. The fasting-triggered galectin-3 elevation was inversely correlated with declines in HOMA-IR and MSS. This may be an evolutionary adaptive survival response that protects human health by modifying disease risks, including by reducing inflammation and insulin resistance. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02770313 (registered on May 12, 2016; first subject enrolled: November 30, 2016; final subject's 26-week study visit: February 19, 2020).

Metabolic Syndrome, Cognitive Impairment and the Role of Diet: A Narrative Review.

BACKGROUND: This narrative review presents the association between metabolic syndrome (MetS), along with its components, and cognition-related disorders, as well as the potential reversal role of diet against cognitive impairment by modulating MetS. METHODS: An electronic research in Medline (Pubmed) and Scopus was conducted. RESULTS: MetS and cognitive decline share common cardiometabolic pathways as MetS components can trigger cognitive impairment. On the other side, the risk factors for both MetS and cognitive impairment can be reduced by optimizing the nutritional intake. Clinical manifestations such as dyslipidemia, hypertension, diabetes and increased central body adiposity are nutrition-related risk factors present during the prodromal period before cognitive impairment. The Mediterranean dietary pattern stands among the most discussed predominantly plant-based diets in relation to cardiometabolic disorders that may prevent dementia, Alzheimer's disease and other cognition-related disorders. In addition, accumulating evidence suggests that the consumption of specific dietary food groups as a part of the overall diet can improve cognitive outcomes, maybe due to their involvement in cardiometabolic paths. CONCLUSIONS: Early MetS detection may be helpful to prevent or delay cognitive decline. Moreover, this review highlights the importance of healthy nutritional habits to reverse such conditions and the urgency of early lifestyle interventions.

Analysis of the SYSDIET Healthy Nordic Diet randomized trial based on metabolic profiling reveal beneficial effects on glucose metabolism and blood lipids.

BACKGROUND & AIMS: Intake assessment in multicenter trials is challenging, yet important for accurate outcome evaluation. The present study aimed to characterize a multicenter randomized controlled trial with a healthy Nordic diet (HND) compared to a Control diet (CD) by plasma and urine metabolic profiles and to associate them with cardiometabolic markers. METHODS: During 18-24 weeks of intervention, 200 participants with metabolic syndrome were advised at six centres to eat either HND (e.g. whole-grain products, berries, rapeseed oil, fish and low-fat dairy) or CD while being weight stable. Of these 166/159 completers delivered blood/urine samples. Metabolic profiles of fasting plasma and 24 h pooled urine were analysed to identify characteristic diet-related patterns. Principal components analysis (PCA) scores (i.e. PC1 and PC2 scores) were used to test their combined effect on blood glucose response (primary endpoint), serum lipoproteins, triglycerides, and inflammatory markers. RESULTS: The profiles distinguished HND and CD with AUC of 0.96 ± 0.03 and 0.93 ± 0.02 for plasma and urine, respectively, with limited heterogeneity between centers, reflecting markers of key foods. Markers of fish, whole grain and polyunsaturated lipids characterized HND, while CD was reflected by lipids containing palmitoleic acid. The PC1 scores of plasma metabolites characterizing the intervention is associated with HDL (ß = 0.05; 95% CI: 0.02, 0.08; P = 0.001) and triglycerides (ß = -0.06; 95% CI: -0.09, -0.03; P < 0.001). PC2 scores were related with glucose metabolism (2 h Glucose, ß = 0.1; 95% CI: 0.05, 0.15; P < 0.001), LDL (ß = 0.06; 95% CI: 0.01, 0.1; P = 0.02) and triglycerides (ß = 0.11; 95% CI: 0.06, 0.15; P < 0.001). For urine, the scores were related with LDL cholesterol. CONCLUSIONS: Plasma and urine metabolite profiles from SYSDIET reflected good compliance with dietary recommendations across the region. The scores of metabolites characterizing the diets associated with outcomes related with cardio-metabolic risk. Our analysis therefore offers a novel way to approach a per protocol analysis with a balanced compliance assessment in larger multicentre dietary trials. The study was registered at clinicaltrials.gov with NCT00992641.

Impact of synbiotic supplementation on cardiometabolic and anthropometric indices in patients with metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Probiotic and synbiotic products are being widely used by a large number of patients and clinicians; however, effects on cardiometabolic indices in patients with the metabolic syndrome remain unclear. This meta-analysis aimed to evaluate the effects of a synbiotic intervention on lipid profile, insulin resistance, blood pressure, anthropometric parameters, and inflammatory markers. METHODS: We searched MEDLINE, Scopus, and Clarivate Analytics Web of Science by October 2021. Studies were selected if they reported the effectiveness of the synbiotic intervention on cardiometabolic and anthropometric indices. The weighted mean difference was calculated as the effect size using a random-effects model. Subgroup analyses were conducted to determine sources of heterogeneity. Dose-dependent effects were assessed using a dose-response meta-analysis of differences in means. RESULTS: Five trials (1049 participants) were finally included in the meta-analysis. Synbiotic intervention significantly reduced serum insulin levels (WMD, -6.39 µU/mL; 95%CI, (-7.2 to -5.4); p = 0.001, I2 = 88.2%, N = 5), triglycerides (WMD, -20.3 mg/dl; 95%CI, (-32.7 to -7.8); p = 0.001, I2 = 87.7, N = 5), total cholesterol (WMD, -7.8 mg/dl; 95%CI, ( -12.5 to -3.02); p = 0.001; I2 = 66.7%, N = 5), low-density lipoprotein cholesterol (WMD, -9.02 mg/dl; 95%CI, (-10.8 to -7.2); p < 0.001, I2 = 0%, N = 5), waist circumference (WMD, -4.04 cm; 95%CI, ( -4.9 to -3.08), p < 0.001; I2 = 22.7%, N = 3), body weight (WMD, -4.3 kg; 95%CI, (-6.2 to -2.5); p = 0.001; I2 = 0%, N = 2), systolic blood pressure (WMD, -1.8 mmHg; 95% CI, (-2.8 to -0.7); p = 0.001; I2 = 0%, N = 3), and serum interleukin-6 concentrations (WMD, -0.2 pg/mL; 95%CI, (-0.3 to -0.08); p = 0.001, I2 = 39.8%, N = 2), and increased high-density lipoprotein cholesterol levels (WMD, 2.3 mg/dl; 95%CI, (0.2-4.4); p = 0.03; 03; I2 = 93.1%, N = 5). Synbiotic administration did not significantly affect fasting plasma glucose, homeostatic model assessment for insulin resistance, body mass index, diastolic blood pressure, heart rate, and serum C-reactive protein concentrations. CONCLUSIONS: The present findings suggest that synbiotic intervention effectively improves cardiometabolic risk factors in patients with metabolic syndrome.

Diet-induced Fasting Ghrelin Elevation Reflects the Recovery of Insulin Sensitivity and Visceral Adiposity Regression.

CONTEXT: Lower fasting ghrelin levels (FGL) are associated with obesity and metabolic syndrome. OBJECTIVE: We aimed to explore the dynamics of FGL during weight loss and its metabolic and adiposity-related manifestations beyond weight loss. METHODS: This was a secondary analysis of a clinical trial that randomized participants with abdominal obesity/dyslipidemia to 1 of 3 diets: healthy dietary guidelines (HDG), Mediterranean diet (MED), or green-MED diet, all combined with physical activity (PA). Both MED diets were similarly hypocaloric and included 28 g/day walnuts. The green-MED group further consumed green tea (3-4 cups/day) and a Wolffia globosa (Mankai) plant green shake. We measured FGL and quantified body fat depots by magnetic resonance imaging at baseline and after 18 months. RESULTS: Among 294 participants (body mass index = 31.3 kg/m2; FGL = 504 ± 208 pg/mL; retention rate = 89.8%), lower FGL was associated with unfavorable cardiometabolic parameters such as higher visceral adipose tissue (VAT), intrahepatic fat, leptin, and blood pressure (P < 0.05 for all; multivariate models). The ∆FGL18-month differed between men (+7.3 ± 26.6%) and women (-9.2% ± 21.3%; P = 0.001). After 18 months of moderate and similar weight loss among the MED groups, FGL increased by 1.3%, 5.4%, and 10.5% in HDG, MED, and green-MED groups, respectively (P = 0.03 for green-MED vs HDG); sex-stratified analysis revealed similar changes in men only. Among men, FGL18-month elevation was associated with favorable changes in insulin resistance profile and VAT regression, after adjusting for relative weight loss (HbA1c: r = -0.216; homeostatic model of insulin resistance: r = -0.154; HDL-c: r = 0.147; VAT: r = -0.221; P < 0.05 for all). Insulin resistance and VAT remained inversely related with FGL elevation beyond that explained by weight loss (residual regression analyses; P < 0.05). CONCLUSION: Diet-induced FGL elevation may reflect insulin sensitivity recovery and VAT regression beyond weight loss, specifically among men. Green-MED diet is associated with greater FGL elevation.

Role of vitamins in the metabolic syndrome and cardiovascular disease.

The prevalence of metabolic syndrome and cardiovascular disease has increased and continues to be the leading cause of mortality worldwide. The etiology of these diseases includes a complex phenotype derived from interactions between genetic, environmental, and nutritional factors. In this regard, it is common to observe vitamin deficiencies in the general population and even more in patients with cardiometabolic diseases due to different factors. Vitamins are essential micronutrients for cellular metabolism and their deficiencies result in diseases. In addition to its role in nutritional functions, increasingly, vitamins are being recognized as modulators of genetics expression and signals transduction, when consumed at pharmacological concentrations. Numerous randomized preclinical and clinical trials have evaluated the use of vitamin supplementation in the prevention and treatment of metabolic syndrome and cardiovascular disease. However, it is controversy regarding its efficacy in the treatment and prevention of these diseases. In this review, we investigated chemical basics, physiological effect and recommended daily intake, problems with deficiency and overdose, preclinical and clinical studies, and mechanisms of action of vitamin supplementation in the treatment and prevention of metabolic syndrome and cardiovascular disease.

Examining the Interaction of the Gut Microbiome with Host Metabolism and Cardiometabolic Health in Metabolic Syndrome.

(1) Background: The microbiota-host cross-talk has been previously investigated, while its role in health is not yet clear. This study aimed to unravel the network of microbial-host interactions and correlate it with cardiometabolic risk factors. (2) Methods: A total of 47 adults with overweight/obesity and metabolic syndrome from the METADIET study were included in this cross-sectional analysis. Microbiota composition (151 genera) was assessed by 16S rRNA sequencing, fecal (m = 203) and plasma (m = 373) metabolites were profiled. An unsupervised sparse generalized canonical correlation analysis was used to construct a network of microbiota-metabolite interactions. A multi-omics score was derived for each cluster of the network and associated with cardiometabolic risk factors. (3) Results: Five multi-omics clusters were identified. Thirty-one fecal metabolites formed these clusters and were correlated with plasma sphingomyelins, lysophospholipids and medium to long-chain acylcarnitines. Seven genera from Ruminococcaceae and a member from the Desulfovibrionaceae family were correlated with fecal and plasma metabolites. Positive correlations were found between the multi-omics scores from two clusters with cholesterol and triglycerides levels. (4) Conclusions: We identified a correlated network between specific microbial genera and fecal/plasma metabolites in an adult population with metabolic syndrome, suggesting an interplay between gut microbiota and host lipid metabolism on cardiometabolic health.

Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model.

Metabolic syndrome (MS) is a risk factor for type 2 diabetes mellitus, vascular inflammation, atherosclerosis, and renal, liver, and heart diseases. Non-alcoholic steatohepatitis (NASH) is a progressive representative liver disease and may lead to the irreversible calamities of cirrhosis and hepatocellular carcinoma. Metabolic disorders such as hyperglycemia have been broadly reported to be related to hepatocarcinogenesis in NASH; however, direct evidence of a link between hyperglycemia and carcinogenesis is still lacking. Tsumura Suzuki Obese Diabetic (TSOD) mice spontaneously develop metabolic syndrome, including obesity, insulin resistance, and NASH-like liver phenotype, and eventually develop hepatocellular carcinomas. TSOD mice provide a spontaneous human MS-like model, even with significant individual variations. In this study, we monitored mice in terms of their changes in blood glucose levels, body weights, and pancreatic and liver lesions over time. As a result, liver carcinogenesis was delayed in non-hyperglycemic TSOD mice compared to hyperglycemic mice. Moreover, at the termination point of 40 weeks, liver tumors appeared in 18 of 24 (75%) hyperglycemic TSOD mice; in contrast, they only appeared in 5 of 24 (20.8%) non-hyperglycemic mice. Next, we investigated three kinds of oligosaccharide that could lower blood glucose levels in hyperglycemic TSOD mice. We monitored the levels of blood and urinary glucose and assessed pancreatic lesions among the experimental groups. As expected, significantly lower levels of blood and urinary glucose and smaller deletions of Langerhans cells were found in TSOD mice fed with milk-derived oligosaccharides (galactooligosaccharides and lactosucrose). At the age of 24 weeks, mild steatohepatitis was found in the liver but there was no evidence of liver carcinogenesis. Steatosis in the liver was alleviated in the milk-derived oligosaccharide-administered group. Taken together, suppressing the increase in blood glucose level from a young age prevented susceptible individuals from diabetes and the onset of NAFLD/NASH, as well as carcinogenesis. Milk-derived oligosaccharides showed a lowering effect on blood glucose levels, which may be expected to prevent liver carcinogenesis.

Serum metabolite profiling yields insights into health promoting effect of A. muciniphila in human volunteers with a metabolic syndrome.

Reduction of A. muciniphila relative abundance in the gut microbiota is a widely accepted signature associated with obesity-related metabolic disorders. Using untargeted metabolomics profiling of fasting plasma, our study aimed at identifying metabolic signatures associated with beneficial properties of alive and pasteurized A. muciniphila when administrated to a cohort of insulin-resistant individuals with metabolic syndrome. Our data highlighted either shared or specific alterations in the metabolome according to the form of A. muciniphila administered with respect to a control group. Common responses encompassed modulation of amino acid metabolism, characterized by reduced levels of arginine and alanine, alongside several intermediates of tyrosine, phenylalanine, tryptophan, and glutathione metabolism. The global increase in levels of acylcarnitines together with specific modulation of acetoacetate also suggested induction of ketogenesis through enhanced ß-oxidation. Moreover, our data pinpointed some metabolites of interest considering their emergence as substantial compounds pertaining to health and diseases in the more recent literature.

MUFA in metabolic syndrome and associated risk factors: is MUFA the opposite side of the PUFA coin?

Omega-9 fatty acids represent some of the main mono-unsaturated fatty acids (MUFA) found in plant and animal sources. They can be synthesized endogenously in the human body, but they do not fully provide all the body's requirements. Consequently, they are considered as partially essential fatty acids. MUFA represent a healthier alternative to saturated animal fats and have several health benefits, including the prevention of metabolic syndrome (MetS) and its complications. This review concentrates on the major MUFA pharmacological activities in the context of MetS management, including alleviating cardiovascular disease (CVD) and dyslipidemia, central obesity, non-alcoholic fatty liver disease (NAFLD), and type 2 diabetes mellitus (T2DM). The beneficial effects of MUFA for CVD were found to be consistent with those of polyunsaturated fatty acids (PUFA) for the alleviation of systolic and diastolic blood pressure and high low density lipoprotein cholesterol (LDLc) and triacylglcerol (TAG) levels, albeit MUFA had a more favorable effect on decreasing night systolic blood pressure (SBP). To reduce the obesity profile, the use of MUFA was found to induce a higher oxidation rate with a higher energy expenditure, compared with PUFA. For NAFLD, PUFA was found to be a better potential drug candidate for the improvement of liver steatosis in children than MUFA. Any advantageous outcomes from using MUFA for diabetes and insulin resistance (IR) compared to using PUFA were found to be either non-significant or resulted from a small number of meta-analyses. Such an increase in the number of studies of the mechanisms of action require more clinical and epidemiological studies to confirm the beneficial outcomes, especially over a long-term treatment period.

The effects of consuming a low-fat yogurt fortified with nano encapsulated vitamin D on serum pro-oxidant-antioxidant balance (PAB) in adults with metabolic syndrome; a randomized control trial.

BACKGROUND AND AIM: The current study aimed to assess the effect of fortified yogurt with nano-encapsulated vitamin D on serum pro-oxidant anti-oxidant balance (PAB) in adults with or without metabolic syndrome. METHODS: In a quadruple blind clinical trial study, 139 adults with an age range of 30-50 years were randomly selected to receive either 1500 IU nano-encapsulated vitamin D fortified yogurt or placebo for ten weeks. Before and after the intervention period, blood sample was taken to determine the serum levels of vitamin D, pro-oxidant-antioxidant balance (PAB), and high-sensitivity C-reactive protein (hs-CRP). The laboratory tests were checked at baseline and at the end of the treatment. RESULTS: Serum vitamin D increased significantly, from 14.47 ± 6.07 ng/mL to 21.39 ± 6.54 ng/mL (P < 0.001) after ten weeks in the intervention group. Serum hs-CRP and PAB were significantly lower following consumption period in intervention group [1.95(0.4-8.15) g/dL vs. 1.35(0.25-3.62) g/dL; P = 0.013] and (135.19 ± 42.4 HK vs. 115.39 ± 44.69) HK; P = 0.018] respectively. There were no significant differences between the intervention and control groups regarding weight and BMI at the end of the intervention period (p > 0.05). CONCLUSION: Low-fat yogurt fortified with nano-encapsulated vitamin D was found to reduce serum PAB levels in adults with metabolic syndrome. PRACTICAL APPLICATION: The findings of the present study indicated that a low-fat yogurt fortified with 1500 IU nano-encapsulated vitamin D for ten weeks, leads to a significant reduction in serum hs-CRP and PAB concentrations highlighted the anti-inflammatory/anti-oxidative effect of vitamin D.

Effects of Nutrients on Platelet Function: A Modifiable Link between Metabolic Syndrome and Neurodegeneration?

Metabolic syndrome increases the risk of vascular dementia and other neurodegenerative disorders. Recent studies underline that platelets play an important role in linking peripheral with central metabolic and inflammatory mechanisms. In this narrative review, we address the activation of platelets in metabolic syndrome, their effects on neuronal processes and the role of the mediators (e.g., serotonin, platelet-derived growth factor). Emerging evidence shows that nutritional compounds and their metabolites modulate these interactions-specifically, long chain fatty acids, endocannabinoids and phenolic compounds. We reviewed the role of activated platelets in neurovascular processes and nutritional compounds in platelet activation.

Coffee Bioactive N-Methylpyridinium Attenuates Tumor Necrosis Factor (TNF)-α-Mediated Insulin Resistance and Inflammation in Human Adipocytes.

Although coffee consumption has been historically associated with negative health outcomes, recent evidence suggests a lower risk of metabolic syndrome, obesity and diabetes among regular coffee drinkers. Among the plethora of minor organic compounds assessed as potential mediators of coffee health benefits, trigonelline and its pyrolysis product N-methylpyridinium (NMP) were preliminary shown to promote glucose uptake and exert anti-adipogenic properties. Against this background, we aimed at characterizing the effects of trigonelline and NMP in inflamed and dysfunctional human adipocytes. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were treated with NMP or, for comparison, trigonelline, for 5 h before stimulation with tumor necrosis factor (TNF)-α. NMP at concentrations as low as 1 µmol/L reduced the stimulated expression of several pro-inflammatory mediators, including C-C Motif chemokine ligand (CCL)-2, C-X-C Motif chemokine ligand (CXCL)-10, and intercellular adhesion Molecule (ICAM)-1, but left the induction of prostaglandin G/H synthase (PTGS)2, interleukin (IL)-1ß, and colony stimulating factor (CSF)1 unaffected. Furthermore, NMP restored the downregulated expression of adiponectin (ADIPOQ). These effects were functionally associated with downregulation of the adhesion of monocytes to inflamed adipocytes. Under the same conditions, NMP also reversed the TNF-α-mediated suppression of insulin-stimulated Ser473 Akt phosphorylation and attenuated the induction of TNF-α-stimulated lipolysis restoring cell fat content. In an attempt to preliminarily explore the underlying mechanisms of its action, we show that NMP restores the expression of the master regulator of adipocyte differentiation peroxisome proliferator-activated receptor (PPAR)γ and downregulates activation of the pro-inflammatory mitogen-activated protein jun N-terminal kinase (JNK). In conclusion, NMP reduces adipose dysfunction in pro-inflammatory activated adipocytes. These data suggest that bioactive NMP in coffee may improve the inflammatory and dysmetabolic milieu associated with obesity.

Efectos de la ingesta de lácteos enriquecidos de forma natural con selenio y omega-3 en una muestra de mujeres posmenopáusicas con síndrome metabólico: un ensayo clínico aleatorizado, triple ciego y controlado con placebo / Effects of the intake of dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids in a sample of postmenopausal women with metabolic syndrome: a randomized, triple-blind, placebo-controlled clinical trial

Introducción: el síndrome metabólico de las mujeres posmenopáusicas puede mejorar con una alimentación saludable. Objetivos: evaluar si una intervención alimentaria con productos lácteos enriquecidos en selenio y ácidos grasos poliinsaturados omega-3 aumenta los niveles de selenio y mejora los factores de riesgo cardiovascular en las mujeres posmenopáusicas con síndrome metabólico. Material y métodos: ensayo clínico aleatorizado, triple ciego y controlado, realizado en atención primaria. Captación: abril 2018, 46 mujeres posmenopáusicas con síndrome metabólico consumidoras habituales de lácteos. Aleatorización: 23 en el grupo de control y 23 en el grupo experimental. Intervención: consumo durante 3 meses de lácteos enriquecidos naturalmente con selenio y ácidos grasos poliinsaturados omega-3 (leche, yogur y queso fresco). Controles: consumo de lácteos convencionales. Variable principal: selenio en plasma; secundarias: criterios del síndrome metabólico. Número de registro 2018/256, Comité de Ética Galicia. Resultados: finalizaron 23 mujeres en el grupo de control y 21 en el grupo de intervención. Aumentó el selenio en el grupo de intervención (7,2 µg/L, IC del 95 %: 3,7/10,8) frente al grupo de control (-4,5 µg/L, IC del 95 %: -8/-1) (p < 0,001) y disminuyó el colesterol unido a lipoproteínas de muy baja densidad (-2,3 mg/dl, IC del 95 %: -5,6/1) respecto al grupo de control (1,9 mg/dl, IC del 95 %: -0,7/4,5) (p = 0,043). Las mujeres del grupo experimental mejoraron respecto a su medición basal en perímetro de cintura (p = 0,010), índice de masa corporal (p = 0,047) y colesterol unido a lipoproteínas de alta densidad (p < 0,001). Conclusiones: una intervención con lácteos enriquecidos naturalmente con selenio y omega-3 en mujeres posmenopáusicas con síndrome metabólico puede mejorar los niveles de selenio en plasma y de colesterol unido a lipoproteínas de muy baja densidad. (AU)

Introduction: metabolic syndrome in postmenopausal women can improve with a healthy diet. Objectives: to evaluate whether a dietary intervention with dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids increases selenium plasma levels and improves cardiovascular risk factors in postmenopausal women with metabolic syndrome. Material and methods: a randomized, triple-blind, controlled clinical trial carried out in GP surgeries. Recruitment: April 2018, 46 postmenopausal women with metabolic syndrome who were frequent dairy consumers. Randomization: 23 in control group and 23 in experimental group. Intervention: consumption of dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids (milk, yogurt, fresh cheese) for three months. Controls took conventional dairy. Primary endpoint: plasma selenium levels; secondary endpoints: metabolic syndrome criteria. Registration number 2018/256, Galicia Ethics Committee. Results: in all, 23 women in the control group and 21 in the intervention group completed the trial. Selenium increased in the intervention group (7.2 µg/L, 95 % CI, 3.7/10.8) compared to the control group (-4.5 µg/L, 95 % CI, -8/-1) (p < 0.001) and very low-density lipoprotein cholesterol decreased (-2.3 mg/dL, 95 % CI, -5.6/1) compared to the control group (1.9 mg/dL, 95 % CI, -0.7/4.5) (p = 0.043). Waist circumference (p = 0.010), body mass index (p = 0.047) and high-density lipoprotein cholesterol (p < 0.001) in the experimental group improved in comparison to baseline measurements. Conclusions: an intervention with dairy products naturally enriched with selenium and omega-3 in a sample of postmenopausal women with metabolic syndrome can improve plasma selenium levels and very low-density lipoprotein cholesterol. (AU)