Background/Objectives: Childhood obesity is a growing global concern linked to metabolic disorders such as nonalcoholic fatty liver disease (NAFLD). Small intestinal bacterial overgrowth (SIBO) may exacerbate these conditions by promoting systemic inflammation and metabolic dysfunction. This review evaluates the prevalence of SIBO in obese children, its association with inflammatory and metabolic markers, and the efficacy of diagnostic and therapeutic strategies. Methods: A systematic search of PubMed, Scopus, and Web of Science (2010-present) was conducted using Boolean operators: ('small intestinal bacterial overgrowth' OR 'SIBO') AND 'prevalence' AND ('low-grade inflammatory markers' OR 'metabolic status') AND 'gut microbiome' AND 'dysbiosis' AND 'obese children'. Results: The data show that SIBO is frequently observed in obese pediatric populations and is associated with gut dysbiosis, impaired nutrient absorption, and reduced production of short-chain fatty acids. These changes contribute to increased intestinal permeability, endotoxemia, and chronic low-grade inflammation. Several microbial taxa have been proposed as biomarkers and therapeutic targets. Diagnostic inconsistencies persist, but treatments such as probiotics, prebiotics, dietary interventions, and selective antibiotics show potential, pending further validation. Conclusions: Early identification and treatment of SIBO with tailored strategies may help reduce metabolic complications and improve outcomes in children with obesity.

With the rapid development of the esports industry, an increasing number of esports athletes face various health issues due to occupational characteristics such as a prolonged sedentary lifestyle, high-intensity training, and multi-cycle competitions. Effectively managing and improving the health status of esports athletes has become an urgent need. As a systematic and multidisciplinary collaborative management strategy, the Integrated Health Management Model has been widely applied to various occupational groups, but its application among esports athletes has not yet been systematically reviewed.

This study adopted a narrative literature review method to collect and analyze the existing literature on the health issues and health management of esports athletes. This study aimed to identify the major health problems of esports athletes and explore the role of the Integrated Health Management Model in improving and preventing these health problems.

This study resulted in two main findings: (1) The main health issues faced by esports athletes include musculoskeletal disorders, visual fatigue, metabolic disorders, and psychological stress; (2) the Integrated Health Management Model, through the integration of physical activity and fitness training, psychological counseling, ergonomic optimization, vision protection, and health education, can effectively alleviate common health problems among esports athletes and promote overall health improvement.

The Integrated Health Management Model can effectively improve the overall health level of esports athletes through the integration and synergy of multiple strategies.

Excessive fructose consumption is a significant driver of metabolic disorders, including obesity, diabetes, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis primarily by promoting insulin resistance and fat accumulation. Ketohexokinase C (KHK-C), a pivotal enzyme in fructose metabolism, catalyzes the phosphorylation of fructose to fructose-1-phosphate, initiating a cascade of downstream metabolic processes. In contrast to glucose metabolism, KHK-C lacks negative feedback regulation, allowing the continuous phosphorylation of fructose, which leads to heightened levels of glucose, glycogen, and triglycerides in the bloodstream and liver. While targeting KHK-C offers a promising therapeutic avenue, no drugs have yet been approved for clinical use. Pfizer's PF-06835919 has progressed to phase II trials, demonstrating a reduction in liver fat and improved insulin sensitivity, while Eli Lilly's LY-3522348 also shows significant potential. Nonetheless, there remains a critical need for the development of novel KHK-C inhibitors that offer improved pharmacokinetics, enhanced efficacy, and superior safety profiles.

In the present study, a comprehensive computational strategy was employed to screen 460,000 compounds from the National Cancer Institute library for potential KHK-C inhibitors. Initially, pharmacophore-based virtual screening was used to identify potential hits, followed by multi-level molecular docking, binding free energy estimation, pharmacokinetic analysis, and molecular dynamics (MD) simulations to further evaluate the compounds. This multi-step approach aimed to identify compounds with strong binding affinity, favorable pharmacokinetic profiles, and high potential for efficacy as KHK-C inhibitors.

Ten compounds exhibited docking scores ranging from -7.79 to -9.10 kcal/mol, surpassing those of the compounds currently undergoing clinical trials, PF-06835919 (-7.768 kcal/mol) and LY-3522348 (-6.54 kcal/mol). Their calculated binding free energies ranged from -57.06 to -70.69 kcal/mol, further demonstrating their superiority over PF-06835919 (-56.71 kcal/mol) and LY-3522348 (-45.15 kcal/mol). ADMET profiling refined the selection to five compounds (1, 2, and 4-6), and molecular dynamics simulations identified compound 2 as the most stable and promising candidate compared to the clinical candidate PF-06835919.

These findings highlight compound 2 as a potent KHK-C inhibitor with predicted pharmacokinetics and toxicity profiles supporting its potential for treating fructose-driven metabolic disorders, warranting further validation.

p-Coumaric acid (CA), a 4-hydroxycinnamic acid derivative, is widely distributed in nature and exerts various beneficial biological effects. However, the effects of CA on metabolic abnormalities triggered by excessive fructose intake, such as dyslipidemia, hyperglycemia, non-alcoholic fatty liver disease (NAFLD), and insulin resistance, have not been sufficiently investigated. Our objective was to investigate whether CA ameliorates high-fructose diet (HFrD)-induced metabolic dysregulation.

Golden Syrian hamsters were randomly assigned to 3 groups and were fed diets containing 60% cornstarch (CON group), 60% fructose (HFrD group), or 60% fructose with CA (0.02%) (HFrD+CA group) for 5 weeks.

HFrD feeding significantly increased the levels of plasma triglyceride, apolipoprotein (apo)-CIII, fasting blood glucose, and homeostatic model assessment insulin resistance, and tended to increase plasma total cholesterol (TC) and low-density lipoprotein/very low-density lipoprotein cholesterol (LDL/VLDL-C) compared with the CON group. In HFrD-fed hamsters, CA supplementation significantly decreased plasma TC, LDL/VLDL-C, apo-CIII, and fasting blood glucose levels. Moreover, CA significantly decreased the hepatic lipid levels and fibrosis induced by HFrD. The plasma and hepatic lipid-lowering effects of CA were associated with decreased enzyme activity and mRNA expression of genes involved in fatty acid, triglyceride, and cholesterol synthesis as well as increased activity of carnitine palmitoyltransferase, a rate-limiting enzyme in fatty acid oxidation, in the liver. CA-treated hamsters also exhibited decreased hepatic gluconeogenic enzyme activity and increased hepatic glycolytic enzyme activity, with mRNA expression changes similar to these activity patterns.

Our findings indicate that CA potentially improves metabolic abnormalities associated with excessive fructose intake, such as hyperglycemia, dyslipidemia, and NAFLD.

Since its discovery, most research on fibroblast growth factor 21 (FGF21) has focused on its antihyperglycemia properties. However, attention has recently shifted towards elucidating the ability of FGF21 to lower circulating lipid levels and ameliorate liver inflammation and steatosis. We here discuss the physiology of FGF21 and its role in lipid metabolism, with a focus on genetics, which has up until now not been fully appreciated.

New developments have uncovered associations of common small-effect variants of the FGF21 gene, such as the single nucleotide polymorphisms rs2548957 and rs838133, with numerous physiological, biochemical and behavioural phenotypes linked to energy metabolism and liver function. In addition, rare loss-of-function variants of the cellular receptors for FGF21 have been recently associated with severe endocrine and metabolic phenotypes. These associations corroborate the findings from basic studies and preliminary clinical investigations into the therapeutic potential of FGF21 for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertriglyceridemia. Furthermore, recent breakthrough research has begun to dissect mechanisms of a potential FGF21 brain-adipose axis. Such inter-organ communication would be comparable to that seen with other potent metabolic hormones. A deeper understanding of FGF21 could prove to be further beneficial for drug development.

FGF21 is a potent regulator of lipid and energy homeostasis and its physiology is currently at the centre of investigative efforts to develop agents targeting hypertriglyceridemia and MASLD.

The study of type 2 diabetes mellitus (T2DM) pathophysiology relies mainly on the use of animal models, the most common of which involves the consumption of high-fat diets comprising 60% calories from fat. Although these models reproduce the onset and most complications associated with T2DM, they do not accurately mimic human dietary patterns, as they lack the addition of carbohydrates such as fructose. This study aimed to develop a C57BL/6 mouse model of T2DM that mimics the disease, as occurs in younger individuals, via a medium-fat diet (34.5% kcal from fat) combined with a 20% fructose solution as drinking water and a single low-dose of streptozotocin (STZ) (100 mg/kg), a diabetogenic drug. At week 20, D + T mice exhibited significant weight gain and elevated fasting blood glucose levels compared with those of control mice and the development of insulin resistance. Similarly, the circulating levels of hepatic enzymes (GPT, GOT, and alkaline phosphatase), total cholesterol, and LDL increased. Multi-organ damage, including reduced pancreatic islet size and number, severe hepatic steatosis, inflammatory infiltration in visceral adipose tissue, and cardiac and renal dysfunction, were also detected. The proposed model replicates T2DM in young mice by combining a medium-fat diet with fructose and STZ.

Background/Objectives: Fructose-driven metabolic disorders, such as obesity, non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and type 2 diabetes, are significant global health challenges. Ketohexokinase C (KHK-C), a key enzyme in fructose metabolism, is a promising therapeutic target. α-Mangostin, a naturally occurring prenylated xanthone, has been identified as an effective KHK-C inhibitor, prompting exploration of its analogs for enhanced efficacy. This study aimed to identify α-Mangostin analogs with improved inhibitory properties against KHK-C to address these disorders. Methods: A library of 1383 analogs was compiled from chemical databases and the literature. Molecular docking, binding free energy calculations, pharmacokinetic assessments, molecular dynamics simulations, and quantum mechani-cal analyses were used to screen and evaluate the compounds. α-Mangostin's binding affinity (37.34 kcal/mol) served as the benchmark. Results: Sixteen analogs demonstrated binding affinities superior to α-Mangostin (from -45.51 to -61.3 kcal/mol), LY-3522348 (-45.36 kcal/mol), and reported marine-derived inhibitors (from -22.74 to -51.83 kcal/mol). Hits 7, 8, 9, 13, and 15 not only surpassed these benchmarks in binding affinity, but also exhibited superior pharmacokinetic properties compared to α-Mangostin, LY-3522348, and marine-derived inhibitors, indicating strong in vivo potential. Among these, hit 8 emerged as the best performer, achieving a binding free energy of -61.30 kcal/mol, 100% predicted oral absorption, enhanced metabolic stability, and stable molecular dynamics. Conclusions: Hit 8 emerged as the most promising candidate due to its superior binding affinity, favorable pharmacokinetics, and stable interactions with KHK-C. These findings highlight its potential for treating fructose-driven metabolic disorders, warranting further experimental validation.

In our pursuit of discovering new antidiabetic agents to manage type 2 diabetes mellitus (T2DM), our approach aimed to identify the bioactive feature/pharmacophore responsible for PPAR-γ expression, as it is accountable for the glucose homeostasis and lipid metabolism. This was achieved by pharmacophore model generation, screening of rationally designed newer thiazolidinedione's library, identifying synthesizing and characterizing the top ten molecules (5a-5j) for their (Invitro & invivo) antidiabetic activity. Preliminary screening of all the ligands by Invitro glucose uptake assay in L6 myotubes (skeletal muscle cell line of rats) revealed compound 5b and 5f stimulated the glucose uptake with 79.29 ± 1.02 % and 74.58 ± 1.02 % respectively compared to pioglitazone with 82.36 ± 0.98 %. This was validated by PPAR-γ TF expression assay, which highlighted a dose dependent increase in transactivation of PPAR-γ. These compounds 5b and 5f were evaluated in fructose induced insulin resistance rat model. Where the treatment with 5b and 5f markedly increased the exogenous clearance of glucose and exogenous insulin via OGTT and ITT respectively, also improved the glucose utilization by significantly increasing content of glycogen and uptake of glucose in rat hemidiaphragm and reversed insulin resistance. Likewise a significant decreased in the VLDL and triglyceride levels was seen in 5b and 5f treated groups compared to insulin resistant (IR) group. It improved glycogenesis by catabolism of glucose and maintained glycaemic control. Similarly it had marked action on enzymatic oxidative biomarkers. Compound 5b displayed better, improved T1/2 (half-life) of 4.21 h and Kel (elimination constant) of 0.381 was noticed in comparison to compound 5f indicating the pharmacokinetic profile. Insilico studies like DFT calculations refined the geometry of 5b and 5f ligands, docking and molecular simulation provided the insights in binding affinity, dynamic behaviour and stability of ligands in PPAR-γ ligand binding domain. MM/GBSA provided the energetics of 5b and 5f in binding pocket. Finally network pharmacology identified ADIPOQ (adiponectin), NR1C3 (PPAR-γ), SLC2A4 (GLUT4), and LEP (leptin) proteins associate with compound 5b and 5f and enriched in Adipocytokine pathway, and PPAR-γ signaling pathway.

Prenatal glucocorticoid overexposure alters the developmental program of fetal reproductive organs and results in numerous changes that can lead to various disorders later in life. Moderate fructose consumption during childhood and adolescence may impair the development and function of reproductive organs. The aim of this study was to investigate the effects of prenatal dexamethasone (Dx) exposure in combination with postnatal fructose overconsumption on testicular development and function in fetal and adult male rat offspring. Pregnant female rats were treated with a subcutaneous injection of Dx at a dose of 0.5 mg/kg/day on gestation days 16, 17, and 18, and the effects on fetal growth and testicular development were analyzed. Spontaneously born male offspring were fed 10% fructose in drinking water until the age of 3 months. Prenatal exposure to Dx led to a reduction in fetal weight and testicular volume. However, testicular development normalized by adulthood, with testosterone levels decreasing. After moderate fructose consumption, impaired redox homeostasis and structural changes in the testicles and decreased testosterone levels were observed, indicating reduced testicular function. The results suggest that the synergistic effect of prenatal Dx exposure and moderate postnatal fructose consumption leads to more deleterious changes in testicular tissue.

There is data about the existence of some endocrine cells in the epithelial layer of the bile duct in humans and rats.

We evaluated Ghrelin-, Insulin-, Glucagon- and Somatostatin-positive cells in peribiliary glands, mast cells, and nerve fibres.

Wistar rats were used for dietary manipulation with a 15% fructose solution for 12 weeks. Tissue samples were elaborated with immunohistochemistry for Insulin, Glucagon, Ghrelin, and Somatostatin. Glucose and lipid parameters were studied.

In treated animals, Ghrelin+ and Insulin+ cells in perybiliary glands (PBGs) were significantly increased. In the male fructose group there was a significant increase of the homeostasis model assessment insulin resistance (HOMA-IR).

Stem/progenitor cells in extrahepatic bile tree (EHBT) could be a source of Insulin-producing cells in metabolic syndrome. Fructose treatment induces the increase of Ghrelin+ and Insulin+ cells in PBGs and the elevation of Insulin and Ghrelin plasma concentration.

The overconsumption of added sugars makes people vulnerable to a myriad of diseases. Several biochemical and developmental assays were performed in the current study to assess the effect of fructose on Drosophila melanogaster and to find substitutes for fructose by comparing it to well-known sweeteners. Drosophila was exposed separately to the same ratio of sugar 9.21% (w/v) of several types of sweeteners (sucrose, fructose, glucose syrup, high-fructose corn syrup and stevia). Results revealed that fructose might induce recombination, whereas stevia lacks genotoxic potential. No developmental delay, growth defects, or neurotoxic effects were recorded for any of the sweeteners. We also observed no striking differences in reactive oxygen species levels. Thus, stevia seems to be an alternative sweetener to fructose that can be consumed to reduce fructose-induced anomalies.

The excessive fructose intake including high-fructose corn syrup (HFCS) may be responsible for increase of obesity occurrence. This study was designed to find potential differences in duodenal fructose transporters on mRNA and protein levels between obese and normal weight children and adolescents.

We performed a cross-sectional study on a group of 106 hospitalized patients aged 12 to 18. Glucose transporter 2 (GLUT2) and glucose transporter 5 (GLUT5) mRNA as well as protein levels (ELISA and Western blot methods) were assessed in duodenal mucosa biopsies of the patients categorized as obese or normal weight. Additionally, the expression of the aforementioned transporters was analyzed in patients based on the presence of insulin resistance (IR) and metabolic syndrome (MS).

In children with obesity, increased duodenal protein levels of GLUT5 (Relative protein GLUT5 expression/ACTB) (0.027 ​± ​0.009 vs. 0.011 ​± ​0.006, p ​< ​0.05) but not GLUT2 as compared with the normal weight group, were revealed. No significant differences in duodenal relative GLUT2 and GLUT5 genes expression between the studied groups were found. There was no relationship between the presence of IR or MS and intestinal mRNA GLUT2 and GLUT5 as well as GLUT2 protein expression.

The upregulation of the duodenal GLUT5 may contribute to obesity occurrence in children and adolescents.

This study aimed to examine the effects of different types of skipped meals on cardiometabolic risk factors (CMRF) in Korean adults.

We analyzed 14,062 adults from the Korea National Health and Nutrition Examination Survey conducted between 2016 and 2018. The irregularity of breakfast, lunch, and dinner consumption was assessed using 24-hour recall data, and we categorized the habit of skipping regular meals into eight types. Multiple linear regression was used to estimate the association between each type of meal skipping and the CMRF. We also presented the estimated effects of individual types of meal skipping on the CMRF based on their predicted values and mean differences.

Korean adults tended to have irregular meal consumption habits when they had one or more of the following characteristics: female sex, under the age of 50 years, middle-high to high household income, high school or college or higher education levels, alcohol consumption, and current smoking. Compared to regular eaters, we have observed significantly higher total cholesterol in the following types of meal skipping: irregular breakfast (IB) (P<0.001), irregular lunch (P=0.005), irregular breakfast and lunch (IBL) (P=0.001), irregular breakfast and dinner (P=0.001); higher low-density lipoprotein-cholesterol in IB (P=0.009); higher triglyceride in IB (P=0.005) and IBL (P=0.034); and higher fasting glucose in IB (P=0.046).

Different types of meal skipping were associated with CMRF. Regular breakfast and lunch consumption should be emphasized to prevent and manage cardiometabolic disorders. However, skipping dinner showed no significant association with CMRF.

Metabolic syndrome has become a significant public health concern. This study aims to investigate the impact of dietary patterns on metabolic syndrome in young adults and how physical activity modulates this effect. A cross-sectional study was conducted at a health management center in Tianjin, China, from September 2022 to March 2023. Participants aged 18-35 years were recruited using convenience sampling. Dietary intake was assessed using a validated food frequency questionnaire. Logistic regression models evaluated associations between these patterns and metabolic syndrome, adjusting for potential confounders. Among 442 participants, four dietary patterns were identified: Legume-Nut, Alcohol-Meat, Sugar-Processed, and Egg-Vegetable. The Legume-Nut dietary pattern was associated with a higher risk of metabolic syndrome (OR = 2.63, 95% CI: 1.08-6.37), while the Egg-Vegetable dietary pattern was associated with a lower risk (OR = 0.26, 95% CI: 0.10-0.70). No significant associations were found for the Sugar-Processed and Alcohol-Meat patterns. Subgroup analysis revealed that the Legume-Nut pattern increased the risk of metabolic syndrome among those with irregular physical activity, whereas the Egg-Vegetable pattern decreased the risk. These findings highlight the significant influence of dietary patterns on the risk of metabolic syndrome in young adults and the modifying effect of regular physical activity, underscoring the need for targeted dietary and lifestyle interventions to prevent metabolic syndrome in this population.

Diabetes mellitus (DM), a major cause of mortality, is characterized by insulin resistance and β-cell dysfunction. The increasing prevalence of DM is linked to lifestyle changes and there is a need for alternative approaches to conventional oral hypoglycemic agents. Polysaccharides, particularly non-starch polysaccharides (NSPs), have been identified as promising hypoglycemic agents. Cereals, especially wheat, are key sources of dietary polysaccharides, with NSPs derived from wheat beer attracting significant interest. This study aimed to investigate the hypoglycemic and hypolipidemic effects of NSPs extracted from wheat beer in STZ-induced diabetic C57BL/6J male mice. The results showed that NSPs extract positively influenced blood glucose regulation, lipid profiles, and liver and kidney functions, by attenuating liver AST and kidney CRE levels in a dose-dependent manner. The NSPs demonstrated anti-oxidative and anti-inflammatory properties, potentially providing significant benefits in managing diabetes and its complications. Moreover, the study revealed the histoprotective effects of NSPs on the liver and pancreas, reducing lipid deposition, necrosis, and inflammation. These findings highlight the multifaceted advantages of NSPs and suggest their potential as effective agents in diabetes management. This study supports the need for further research into the therapeutic potential of NSPs and their application in developing innovative treatments for diabetes and its associated complications.

The global prevalence rate of diabetes in 2021 was 6.1% making diabetes one of the top 10 causes of death. Prolonged use of antidiabetic medications is associated with various side effects; therefore, alternative treatment strategies for diabetes need exploration. The antidiabetic properties of Lactiplantibacillus plantarum 2034 was explored both in in vitro and in vivo studies. Secretory metabolites of probiotic L. plantarum 2034 exhibited alpha-glucosidase, alpha-amylase, and lipase inhibitory activities, in vitro. Further, the antidiabetic efficacy of 2034 was evaluated in streptozotocin-nicotinamide-induced diabetic rats. In the therapeutic model, oral administration of L. plantarum resulted in normalization of body weight, fasting blood glucose, total cholesterol (TC), and liver enzymes, and significant (p < 0.05) reduction in insulin and triglyceride (TG) levels. Histological evaluation of pancreas, liver, and kidney showed restoration of normal architecture in probiotic-treated group. Similarly, in a preventive + therapeutic model, 14 days of pre-administration of 2034 in pre, pre + post, and cell-free supernatant resulted in significant reduction in glucose, TG, TC, and liver biochemistry of diabetic rats as compared to untreated diabetic rats. An oral glucose tolerance test showed that the glucose levels normalized within 90 min in all the treated groups. Further, the oxidative stress parameters were also studied that showed that in all the treated groups, the concentration of antioxidant enzymes significantly (p < 0.05) increased as compared to diabetic untreated rats. Thus, administration of L. plantarum 2034 and its metabolites successfully ameliorated hyperglycaemia and hypercholesterolemia in both the models probably due to inhibition of gut enzymes and by increasing the concentration of liver antioxidant enzymes.

Serum uric acid (SUA) has garnered an increased interest in recent years as an important determinant of cardiovascular disease. Uric acid, a degradation product of purine metabolism, is affected by several inheritable and acquired factors, such as genetic mutation, metabolic syndrome, chronic kidney disease, and medication interactions. Even though elevated SUA have been commonly associated with the development of gout, it has significant impact in the development of hypertension, metabolic syndrome, and cardiovascular disease. Uric acid, in both crystalline and soluble forms, plays a key role in the induction of inflammatory cascade and development of atherosclerotic diseases. This concise reappraisal emphasizes key features about the complex and challenging role of uric acid in the development and progression of atherosclerosis and cardiovascular disease. It explores the pathogenesis and historical significance of uric acid, highlights the complex interplay between uric acid and components of metabolic syndrome, focuses on the pro-inflammatory and pro-atherogenic effects of uric acid, as well as discusses the role of urate lowering therapies in mitigating the risk of cardiovascular disease while providing the latest evidence to the healthcare professionals focusing on the clinical importance of SUA levels with regards to cardiovascular disease.

We investigated circulating homocysteine (Hcy), a cardiovascular disease (CVD) risk factor, examining its dietary associations to provide personalized nutrition advice. This study addressed the inadequacy of current dietary interventions to ultimately address the disproportionately high incidence of CVD in Black populations.

Cross-sectional analyses of 1,867 Black individuals of the PURE-SA study allowed the identification of dietary intake and cardiovascular measure interactions on three sub-categories: (1) normal blood pressure (BP), hypertension or Hcy-related hypertension (H-type), (2) low, normal or high Hcy concentrations, and (3) Hcy-related genetic combinations. Favorable body composition, but adverse dietary intake and cardiovascular determinants, were observed in higher Hcy categories. H-types, compared to regular hypertensives, had higher alcohol and lower macronutrient and micronutrient consumption. Inverse associations with carotid-radial pulse wave velocity were evident between monounsaturated fatty acid (FA) consumption and H-type hypertension as well as polyunsaturated FA and CBS883/ins68 TT carriers. Energy intake was positively associated with vascular cell adhesion molecule-1 (VCAM-1) in variant CBST883C/ins68 and CBS9276 GG carriers. VCAM-1 was also positively associated with plant protein intake in CBS9276 GG and MTR2756 AA carriers and negatively with total protein intake and CBS9276 GG carriers. Alcohol intake was positively associated with intercellular adhesion molecule-1 in MTR2756 minor allele carriers.

Because Hcy gene-diet interactions are evident, personalized nutrition, by adjusting diets based on genetic profiles (e.g., CBS and MTR variations) and dietary interactions (e.g., FAs and proteins), can enhance cardiovascular outcomes by managing Hcy and related hypertension in genetically susceptible individuals.

The role of silymarin in hepatic lipid dysfunction and its possible mechanisms of action were investigated.

To evaluate the effects of silymarin on hepatic and metabolic profiles in mice fed with 30% fructose for 8 weeks.

We evaluated the antioxidant profile of silymarin; mice consumed 30% fructose and were treated with silymarin (120 mg/kg/day or 240 mg/kg/day). We performed biochemical, redox status, and histopathological assays. RT-qPCR was performed to detect ACC-1, ACC-2, FAS, and CS expression, and western blotting to detect PGC-1α levels.

Silymarin contains high levels of phenolic compounds and flavonoids and exhibited significant antioxidant capacity in vitro. In vivo, the fructose-fed groups showed increased levels of AST, ALT, SOD/CAT, TBARS, hepatic TG, and cholesterol, as well as hypertriglyceridaemia, hypercholesterolaemia, and increased ACC-1 and FAS. Silymarin treatment reduced these parameters and increased mRNA levels and activity of hepatic citrate synthase.

These results suggest that silymarin reduces worsening of NAFLD.

To date, the risk of developing atherosclerosis has extended beyond Western countries and now affecting individuals from various ethnic backgrounds and age groups. Traditional risk factors of atherosclerosis, such as hypercholesterolemia, has been better controlled than before due to highly effective and inexpensive therapies at lowering plasma cholesterol levels. However, the role of reducing dietary cholesterol intake, as a public healthy strategy, in preventing the occurrence of cardiovascular mortalities has been recently challenged. Indeed, despite our continuous decline of dietary cholesterol intake within the last 50 years, the incidence of cardiovascular mortalities has continued to rise, thus raising the possibility that other dietary factors, such as fructose-containing sugars, are the major culprit. In the 1970s, John Yudkin first proposed that sugar was the predominant dietary factor that underlies the majority of cardiovascular mortalities, yet his hypothesis was dismissed. However, over the last 25 years substantial scientific evidence has been accumulated to support Yudkin's hypothesis. The objectives of this review are to highlight Yudkin's significant contribution to nutritional science by reviewing his hypothesis and summarizing the recent advances in our understanding of fructose metabolism. The metabolic consequences of fructose metabolism, such as fructose-induced uricemia, insulin resistance, lipoprotein hyperproduction and chronic inflammation, and how they are linked to atherosclerosis as risk factors will be discussed. Finally, the review will explore areas that warrant future research and raise important considerations that we need to evaluate when designing future studies.

Dietary fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) contribute to gastrointestinal (GI) symptoms in individuals with FODMAP sensitivity and irritable bowel syndrome. Oral enzyme supplementation is a strategy to reduce dietary FODMAP exposure and limit FODMAP-associated GI distress. This clinical trial investigated the safety of dietary supplementation with a food-grade, microbial inulinase known to hydrolyze fructan-type or inulin-type FODMAPs and related fructo-oligosaccharides in vitro.

A randomized, double-blind, placebo-controlled, parallel design trial was conducted in 60 healthy adult participants of both sexes. Following a 2-week run-in placebo phase, participants were randomized to consume inulinase or placebo capsules twice daily with meals for 4 weeks. The total daily dose of inulinase was 2000 inulinase activity units. Safety measures included blood clinical chemistry, hematology, lipid profile, high-sensitivity C-reactive protein, insulin, lactate, and uric acid. GI symptoms were recorded weekly using the 15-item Gastrointestinal Symptom Rating Scale.

Fifty-eight participants completed the study. There were no clinically meaningful between-group differences in blood biomarkers. During the 4-week intervention period, 5 (16.7%) of 30 participants reported 5 adverse events in the inulinase group, and 8 (26.7%) of 30 participants reported 13 adverse events in the placebo group. No statistically significant between-group differences were observed in the change from baseline to 1, 2, 3, or 4 weeks of supplementation with respect to the 15-item Gastrointestinal Symptom Rating Scale overall or domain scores.

Microbial inulinase supplementation demonstrated a favorable safety profile in healthy adults. Further investigation in a dose-ranging study in individuals with dietary FODMAP, fructan, or inulin sensitivity or irritable bowel syndrome is warranted. ClinicalTrials.gov: NCT05744700.

Worldwide, childhood obesity cases continue to rise, and its prevalence is known to increase the risk of non-communicable diseases typically found in adults, such as cardiovascular disease and type 2 diabetes mellitus. Thus, comprehending its multiple causes to build healthier approaches and revert this scenario is urgent. Obesity development is strongly associated with high fructose intake since the excessive consumption of this highly lipogenic sugar leads to white fat accumulation and causes white adipose tissue (WAT) inflammation, oxidative stress, and dysregulated adipokine release. Unfortunately, the global consumption of fructose has increased dramatically in recent years, which is associated with the fact that fructose is not always evident to consumers, as it is commonly added as a sweetener in food and sugar-sweetened beverages (SSB). Therefore, here, we discuss the impact of excessive fructose intake on adipose tissue biology, its contribution to childhood obesity, and current strategies for reducing high fructose and/or free sugar intake. To achieve such reductions, we conclude that it is important that the population has access to reliable information about food ingredients via food labels. Consumers also need scientific education to understand potential health risks to themselves and their children.

Diabetes might be associated with increased cancer risk, with several studies reporting hyperglycemia as a primary oncogenic stimulant. Since glucose metabolism is linked to numerous metabolic pathways, it is difficult to specify the mechanisms underlying hyperglycemia-induced cancer progression. Here, we focused on the polyol pathway, which is dramatically activated under hyperglycemia and causes diabetic complications. We investigated whether polyol pathway-derived fructose facilitates hyperglycemia-induced gastric cancer metastasis. We performed bioinformatics analysis of gastric cancer datasets and immunohistochemical analyses of gastric cancer specimens, followed by transcriptomic and proteomic analyses to evaluate phenotypic changes in gastric cancer cells. Consequently, we found a clinical association between the polyol pathway and gastric cancer progression. In gastric cancer cell lines, hyperglycemia enhanced cell migration and invasion, cytoskeletal rearrangement, and epithelial-mesenchymal transition (EMT). The hyperglycemia-induced acquisition of metastatic potential was mediated by increased fructose derived from the polyol pathway, which stimulated the nuclear ketohexokinase-A (KHK-A) signaling pathway, thereby inducing EMT by repressing the CDH1 gene. In two different xenograft models of cancer metastasis, gastric cancers overexpressing AKR1B1 were found to be highly metastatic in diabetic mice, but these effects of AKR1B1 were attenuated by KHK-A knockdown. In conclusion, hyperglycemia induces fructose formation through the polyol pathway, which in turn stimulates the KHK-A signaling pathway, driving gastric cancer metastasis by inducing EMT. Thus, the polyol and KHK-A signaling pathways could be potential therapeutic targets to decrease the metastatic risk in gastric cancer patients with diabetes.

Adjuvant therapy is often used to optimize the antihyperlipidemic effect of simvastatin. Omega-3 and vitamin D supplementation are recommended as adjuvant therapies to low-intensity statins. This study aimed to compare the effects of vitamin D and omega-3 as adjuvant therapy to simvastatin to improve the lipid profiles and atherogenic index of plasma (AIP) in type-I dyslipidemic rats.

Thirty-six male rats were randomized and divided into six groups: healthy control, dyslipidemic rats with no treatment, and dyslipidemic rats treated with either low-dose simvastatin only or omega-3 or vitamin D at low and high doses. Dyslipidemia was induced with high-fat diets for four weeks, followed by treatment for the next two weeks. Blood samples were withdrawn before and after simvastatin treatment. In addition, aspartate transaminase (AST) and alanine transaminase (ALT) levels were analyzed to assess liver function.

Administration of a high-fat diet-induced type 1 dyslipidemia and increased ALT levels (p < 0.05). Treatment with low-dose simvastatin did not significantly improve triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc) or non-HDLc levels. When combined with a high-dose vitamin D, simvastatin significantly reduced TG and increased HDLc levels (p < 0.05), thereby improving AIP levels. This improvement was not observed in rats treated with omega-3 or vitamin D at a lower dose.

We concluded that high-dose vitamin D as an adjuvant to simvastatin therapy was superior to omega-3 in improving TG, HDL, and AIP levels. High-dose vitamin D also improved ALT levels in type-I dyslipidemic rats. This result may be translated in clinics to reduce the risk of coronary syndrome in patients with type-I dyslipidemia.

Hypertension is a major cardiac risk factor. Higher blood pressures are becoming more prevalent due to changing dietary habits. Here, we evaluated the impact on blood pressure in human subjects after acutely ingesting fructose using meta-analysis. A total of 89 studies were collected from four different electronic databases from 1 January 2008 to 1 August 2023. Of these studies, 10 were selected that fulfilled all the criteria for this meta-analysis. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), and blood glucose level were analyzed using the Cohen's d analysis or standardized mean difference at a confidence interval (CI) of 95%. The SBP, DBP, and MAP showed medium effect size; HR and glucose level displayed small effect size. The standardized mean difference of normal diet groups and fructose diet groups showed a significant increase in SBP (p = 0.04, REM = 2.30), and DBP (p = 0.03, REM = 1.48) with heterogeneity of 57% and 62%, respectively. Acute fructose ingestion contributes to an increase in arterial pressure in humans. The different parameters of arterial pressure in humans correlated with each other. These findings support further rigorous investigation, retrospective of necessity, into the effect of chronic dietary of fructose in humans in order to better understand the impact on long term arterial pressure.

Chronic diseases and metabolic disorders are prevalent health concerns that often escalate with increasing age and thus affect older individuals. The proportion of the elderly population in Iran increased from 7.22% in 2006 to 12.0% in 2023. The current study aimed to evaluate lifestyle patterns and lifestyle risk factors among patients with metabolic syndrome (MetS) based on dietary, physical activity, and smoking, as well as MetS components.

This cross-sectional study included 582 older people with MetS living in Yazd, Iran. Latent class analysis (LCA) was used to determine the lifestyle behaviors of diet patterns, smoking, and physical activity. Dietary intake was measured using a validated food frequency questionnaire, and dietary patterns were identified using principal component analysis (PCA). Clinical measurements of MetS components were examined using relevant guidelines.

The mean age of the participants was 72.71 years (SD = 5.57). Using PCA, two dietary patterns were identified: traditional patterns (e.g., fruits, fish, poultry, vegetables, meats, salt, and sugar sweetened beverages) and high-fat patterns (e.g., high-fat dairy). Applying LCA identified two classes of lifestyle patterns. About 35% (n = 204) of the participants were categorized in a low-risk class (I) and characterized by physical activity (0.93%, n = 190), a traditional pattern for diet (61%, n = 122), and zero probability of smoking. About 65% (n = 378) of the patients were categorized in high-risk class (II) and characterized by low physical activity levels (69%, n = 261), cigarette smoking (71.6%, n = 271), and a high-fat dietary pattern (56.9%, n = 215).

The results of our study indicated two distinct classes within the patients. In class I, aging patients with MetS exhibited characteristics such as engagement in physical activity and having a traditional pattern for diet. Class II, with a higher prevalence of lifestyle risk factors, included individuals who engaged in cigarette smoking, displayed low physical activity (69%), and having a high-fat diet. The combination of these lifestyle factors exposed them to a heightened risk of developing MetS. The findings could guide healthcare professionals to be aware of the associations between different lifestyle risk factors and to focus on multiple behaviors at the same time.

Type 2 diabetes is a non-communicable metabolic syndrome that is characterized by the dysfunction of pancreatic β-cells and insulin resistance. Both animal and human studies have been conducted, demonstrating that helminth infections are associated with a decreased prevalence of type 2 diabetes mellitus (T2DM). However, there is a paucity of information on the impact that helminths have on the metabolome of the host and how the infection ameliorates T2DM or its progression. Therefore, this study aimed at using a non-targeted metabolomics approach to systematically identify differentiating metabolites from serum samples of T2DM-induced Sprague Dawley (SD) rats infected with a tissue-dwelling nematode, Trichinella zimbabwensis, and determine the metabolic pathways impacted during comorbidity. Forty-five male SD rats with a body weight between 160 g and 180 g were used, and these were randomly selected into control (non-diabetic and not infected with T. zimbabwensis) (n = 15) and T2DM rats infected with T. zimbabwensis (TzDM) (n = 30). The results showed metabolic separation between the two groups, where d-mannitol, d-fructose, and glucose were upregulated in the TzDM group, when compared to the control group. L-tyrosine, glycine, diglycerol, L-lysine, and L-hydroxyproline were downregulated in the TzDM group when compared to the control group. Metabolic pathways which were highly impacted in the TzDM group include biotin metabolism, carnitine synthesis, and lactose degradation. We conclude from our study that infecting T2DM rats with a tissue-dwelling nematode, T. zimbabwensis, causes a shift in the metabolome, causing changes in different metabolic pathways. Additionally, the infection showed the potential to regulate or improve diabetes complications by causing a decrease in the amino acid concentration that results in metabolic syndrome.

The present systematic review of animal studies on long-term fructose intake in rodents revealed a significant decrease in the activities of antioxidant enzymes due to a fructose-rich diet. The reduced activity of these enzymes led to an increase in oxidative stress, which can cause liver damage in rodents. Of eight studies analyzed, 5 (62.5%) and 1 (12.5%) used male and female rats, respectively, while 2 studies (25%) used female mice. Moreover, half of the studies used HFCS, but the other half employed fructose in the diet. Hence, it is essential to monitor dietary habits to ensure public health and nutrition research outcomes.

Hepatic steatosis is an important mstetabolic complication in women encountering postmenopausal phase of life. Pancreastatin (PST), has previously been investigated in diabetic and insulin resistant rodents. The present study highlighted the role of PST in ovariectomized rats. Female SD rats were ovariectomized and subsequently fed high fructose diet for 12 weeks. PST inhibitor peptide was intraperitoneally administered for 14 days and further examined for insulin resistance, glucose intolerance development, body mass composition, lipid profile detection and hepatic fibrosis. Gut microbial alterations has also been investigated. Results showed development of glucose intolerance in high fructose fed ovariectomized rats with reduced level of reproductive hormones including estradiol and progesterone. Enhanced lipid production was detected in these rats as they showed increased triglycerides, lipid accumulation in liver tissue (determined by HE staining, Oil Red O staining, Nile Red staining). Sirius Red and Masson's trichome analysis depicted positive results for fibrosis development. We also found gut microbiota alterations in fecal samples of these rats. Furthermore, PST inhibition decreased the expression of hepatic Fetuin B and resumed gut microbial diversity. PST deregulates hepatic lipid metabolism which leads to altered expression of Fetuin B in liver and gut dysbiosis in postmenopausal rats.

Type 2 diabetes mellitus (DM) is a common chronic condition characterized by persistent hyperglycemia and is associated with insulin resistance (IR) in critical glucose-consuming tissues, including skeletal muscle and adipose tissue. Oxidative stress and mitochondrial dysfunction are known to play key roles in IR. Acrolein is a reactive aldehyde found in the diet and environment that is generated as a fatty acid product through the glucose autooxidation process under hyperglycemic conditions. Our previous studies have shown that acrolein impairs insulin sensitivity in normal and diabetic mice, and this effect can be reversed by scavenging acrolein. This study demonstrated that acrolein increased oxidative stress and inhibited mitochondrial respiration in differentiated C2C12 myotubes and differentiated 3T3-L1 adipocytes. As a result, insulin signaling pathways were inhibited, leading to reduced glucose uptake. Treatment with acrolein scavengers, N-acetylcysteine, or carnosine ameliorated mitochondrial dysfunction and inhibited insulin signaling. Additionally, an increase in acrolein expression correlated with mitochondrial dysfunction in the muscle and adipose tissues of diabetic mice. These findings suggest that acrolein-induced mitochondrial dysfunction contributes to IR, and scavenging acrolein is a potential therapeutic approach for treating IR.

Eupafolin is a phyto compound of flavone that exerts anti-inflammatory, antioxidant, and antiproliferative properties. The main purpose of this study is to examine the antidiabetic effect of eupafolin on nicotinamide-streptozotocin (STZ)-induced Type 2 diabetes (T2D) rats. After nicotinamide (120 mg/kg) treatment, STZ (60 mg/kg) was administrated intravenously to induce T2D. Rats with fasting blood glucose (FBG) > 200 mg/dL are chosen for the study 7 days after T2D induction. The eupafolin treatment was continued for another 15 days. FBG and an oral glucose tolerance test (OGTT) were measured on the 21st day after T2D induction. The blood lipid, serum insulin, and homeostatic model assessment (HOMA-IR) were determined. In liver homogenate, oxidative stress indicators were measured. In addition, the effect of eupafolin on the expression of the proteins InsR, insulin receptor substrate (IRS)-2, GLUT4, PPARγ, and phosphatidylinositol 3-kinase (PI3K)/Akt was investigated using a western blot. As measured by OGTT and HOMA-IR, eupafolin treatment reduced FBG and insulin resistance (IR). Furthermore, when compared to diabetic rats, liver antioxidant enzymes were dramatically normalized. The level of glycogen in the liver of diabetic rats was increased by eupafolin treatment. In T2D rats, eupafolin dramatically increased the InsR, IRS-2, GLUT4, and PPARγ. Further, the eupafolin treatment activated the PI3K/Akt signaling in T2D rats. These findings imply that the antidiabetic mechanism of eupafolin may be related to the activation of the PPARγ and the PI3K/Akt signaling pathway in T2D rats. As a result, the flavonoid eupafolin could be an antidiabetic medication for T2D after a comprehensive clinical investigation.

The predisposition of humans to metabolic syndrome is affected by many factors, including diet and lifestyle. Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are a set of carbohydrates that are fermented by gut microbiota. In animal studies, supplementation with FODMAP-rich diets as prebiotics can alter body composition and gut microbiota. This study evaluates any relationship between FODMAP and metabolic syndrome risk factors among adults with metabolic syndrome in Iran.

This cross-sectional study is based on sociodemographic information from 347 overweight and obese participants selected from outpatient clinics through public declaration. Participants body composition and anthropometric measures were also determined. A validated Food Frequency Questionnaire (FFQ) with 168 questions was used to collect dietary data. Biochemical parameters, including serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), fasting serum glucose (FSG), and insulin levels, were determined by enzymatic methods. In addition, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated.

In moderate FODMAP and low FODMAP groups, lower waist-to-hip ratio (WHR) and higher fat-free mass (FFM) were achieved in higher tertiles. In high FODMAP groups, higher systolic blood pressure (SBP) was shown in the higher tertile (P < 0.05). Higher insulin, HOMA-IR, and lower QUICKI in the second tertile of the high FODMAP group were also observed.

Findings of this study highlight the potential role of FODMAP in managing metabolic syndrome and open a new field of research.

L-Arginine and chronic exercise reduce oxidative stress. However, it is unclear how they affect cardiomyocytes during cardiovascular disease (CVD) development. The aim of this research was to investigate the possible effects of L-arginine supplementation and aerobic training on systemic oxidative stress and their consequences on cardiomyocytes during cardiometabolic disease onset caused by excess fructose. Wistar rats were allocated into four groups: control (C), fructose (F, 10% fructose in water), fructose training (FT; moderate running, 50-70% of the maximal velocity), and fructose arginine (FA; 880 mg/kg/day). Fructose was given for two weeks and fructose plus treatments for the subsequent eight weeks. Body composition, blood glucose, insulin, lipid profile, lipid peroxidation, nitrite, metalloproteinase-2 (MMP-2) activity, left ventricle histological changes, microRNA-126, -195, and -146, eNOS, p-eNOS, and TNF-α expressions were analyzed. Higher abdominal fat mass, triacylglycerol level, and insulin level were observed in the F group, and both treatments reversed these alterations. Myocardial vascularization was impaired in fructose-fed groups, except in FT. Cardiomyocyte hypertrophy was observed in all fructose-fed groups. TNF-α levels were higher in fructose-fed groups than in the C group, and p-eNOS levels were higher in the FA than in the C and F groups. Lipid peroxidation was higher in the F group than in the FT and C groups. During CVD onset, moderate aerobic exercise reduced lipid peroxidation, and both training and L-arginine prevented metabolic changes caused by excessive fructose. Myocardial vascularization was impaired by fructose, and cardiomyocyte hypertrophy appeared to be influenced by pro-inflammatory and oxidative environments.

Type 2 diabetes (T2D) is a growing public health burden throughout the world. Many people looking for information on how to prevent T2D will search on diabetes websites. Multiple dietary factors have a significant association with T2D risk, such as high intake of added sugars, refined carbohydrates, saturated fat, and red meat or processed meat; and decreased intake of dietary fiber, and fruits/vegetables. Despite this dietary information being available in the scientific literature, it is unclear whether this information is available in gray literature (websites).

In this study, we evaluate the use of specific terms from diabetes websites that are significantly associated with causes/risk factors and preventions for T2D from three term categories: (A) dietary factors, (B) nondietary nongenetic (lifestyle-associated) factors, and (C) genetic (non-modifiable) factors. We also evaluate the effect of website type (business, government, nonprofit) on term usage among websites.

We used web scraping and coding tools to quantify the use of specific terms from 73 diabetes websites. To determine the effect of term category and website type on the usage of specific terms among 73 websites, a repeated measures general linear model was performed.

We found that dietary risk factors that are significantly associated with T2D (e.g., sugar, processed carbohydrates, dietary fat, fruits/vegetables, fiber, processed meat/red meat) were mentioned in significantly fewer websites than either nondietary nongenetic factors (e.g., obesity, physical activity, dyslipidemia, blood pressure) or genetic factors (age, family history, ethnicity). Among websites that provided "eat healthy" guidance, one third provided zero dietary factors associated with type 2 diabetes, and only 30% provided more than two specific dietary factors associates with type 2 diabetes. We also observed that mean percent usage of all terms associated with T2D causes/risk factors and preventions was significantly lower among government websites compared to business websites and nonprofit websites.

Diabetes websites need to increase their usage of dietary factors when discussing causes/risk factors and preventions for T2D; as dietary factors are modifiable and strongly associated with all nondietary nongenetic risk factors, in addition to T2D risk.

Honey is a nutritious, healthy, and natural food, to which antioxidant, anti-inflammatory, and antimicrobial properties have been attributed, mainly due to its content of phenolic compounds. The aim of this review is to analyze the available evidence of the effect of honey on humans. Forty-eight clinical trials published between 1985 and 2022 were analyzed, with a total of 3655 subjects. More beneficial effects of honey intake than no or negative effects on different cardiovascular and metabolic risk factors, glucose tolerance, mucositis caused by chemo-radiotherapy, cough in children and wound healing, among others have been observed. Although the number of studies conducted to date is limited and the different investigations are not standardized, beneficial effects of honey intake have been observed, especially when its intake replaces the intake of other sweeteners. In addition, honey could be a safe adjuvant to be administered alongside drugs used for certain diseases.

Research has found that genes specific to microglia are among the strongest risk factors for Alzheimer's disease (AD) and that microglia are critically involved in the etiology of AD. Thus, microglia are an important therapeutic target for novel approaches to the treatment of AD. High-throughput in vitro models to screen molecules for their effectiveness in reversing the pathogenic, pro-inflammatory microglia phenotype are needed. In this study, we used a multi-stimulant approach to test the usefulness of the human microglia cell 3 (HMC3) cell line, immortalized from a human fetal brain-derived primary microglia culture, in duplicating critical aspects of the dysfunctional microglia phenotype. HMC3 microglia were treated with cholesterol (Chol), amyloid beta oligomers (AβO), lipopolysaccharide (LPS), and fructose individually and in combination. HMC3 microglia demonstrated changes in morphology consistent with activation when treated with the combination of Chol + AβO + fructose + LPS. Multiple treatments increased the cellular content of Chol and cholesteryl esters (CE), but only the combination treatment of Chol + AβO + fructose + LPS increased mitochondrial Chol content. Microglia treated with combinations containing Chol + AβO had lower apolipoprotein E (ApoE) secretion, with the combination of Chol + AβO + fructose + LPS having the strongest effect. Combination treatment with Chol + AβO + fructose + LPS also induced APOE and TNF-α expression, reduced ATP production, increased reactive oxygen species (ROS) concentration, and reduced phagocytosis events. These findings suggest that HMC3 microglia treated with the combination of Chol + AβO + fructose + LPS may be a useful high-throughput screening model amenable to testing on 96-well plates to test potential therapeutics to improve microglial function in the context of AD.

Feronia elephantum corr. (synonym: Feronia limonia, Murraya odorata, Schinus Limonia, or Limonia acidissima; common names: Bela, Kath, Billin, and Kavitha), belonging to the family Rutaceae has been known for clinical conditions such as pruritus, diarrhea, impotence, dysentery, heart diseases, and is also used as a liver tonic. However, the effect of the fruit pulp of F. elephantum on insulin resistance has yet not been reported.

The present study aimed to assess the effect of hydroalcoholic extract/fraction of F. elephantum fruit pulp on fasting blood glucose, oral glucose tolerance test, and glucose uptake in fructose-induced insulin-resistant rats and predict the gene-set enrichment of lead hits of F. elephantum with targets related to insulin resistance.

System biology tools were used to predict the best category of fraction and propose a possible mechanism. Docking was carried out with adiponectin and its receptor (hub gene). Further, fructose supplementation was used for the induction of insulin resistance. Later, three doses of extract (400, 200, and 100 mg/kg) and a flavonoid-rich fraction (63 mg/kg) were used for treatment along with metformin as standard. The physical parameters like body weight, food intake, and water intake were measured along with oral glucose tolerance test, insulin tolerance test, glycogen content in skeletal muscles and liver, glucose uptake by rat hemidiaphragm, lipid profiles, anti-oxidant biomarkers, and histology of the liver and adipose tissue.

Network pharmacology reflected the potency of F. elephantum to regulate adiponectin (ADIPOQ) which may promote the reversal of insulin resistance and inhibit α-amylase and α-glucosidase. Vitexin was predicted to modulate the most genes associated with diabetes mellitus. Further, F. elephantum ameliorated the exogenous glucose clearance, promoted insulin sensitivity, reduced oxidative stress, and improved glucose and lipid metabolism. HPLC profiling revealed the presence of apigenin and quercetin in the extract for the first time.

The fruit pulp of F. elephantum reverses insulin resistance by an increase in glucose uptake and a decrease in gluconeogenesis which may be due to the regulation of multiple proteins via multiple bio-actives.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, insulin resistance, and insufficient insulin secretion. It is considered that chronic hyperglycemia causes serious problems due to diabetic complications such as retinopathy, nephropathy, and neuropathy. Primarily, treatment in T2DM is pharmacologically tried by using drugs that are insulin sensitizers, insulin secretagogues, α-glucosidase inhibitors, and glucose transporter inhibitors. However, long-term application of these drugs frequently induces various harmful side effects, suggesting that the importance of taking advantage of natural products like phytochemicals. Accordingly, flavonoids, a group of phytochemicals, have attracted attention as components of natural products which are effective in the treatment of several diseases containing T2DM and are strongly recommended as food supplements to ameliorate T2DM-related complications. Several well-studied flavonoids such as quercetin and catechin are known to have anti-diabetic, anti-obesity, and anti-hypertensive actions, although a huge number of flavonoids are still under investigation and their actions are not fully understood. In this situation, myricetin is being shown to be a multiple bioactive compound to prevent and/or suppress hyperglycemia through inhibiting digestion and uptake of saccharides and enhancing insulin secretion as a possible GLP-1 receptor agonist, and to ameliorate T2DM-related complications by protecting endothelial cells from oxidative stress induced by hyperglycemia. In this review, we summarize the multiple effects of myricetin on the targets of T2DM treatment, comparing with different flavonoids.

Reduced meal frequency can increase the risk of metabolic syndrome (MetS). However, limited studies have examined the association between meal frequency and skipping meals with MetS. This study aims to analyze the association between main meal frequency and meal skipping with MetS in Korean adults aged ≥ 19 years.

In this study, we included data from 22,699 Korean adult participants from the 2016-2020 Korea National Health and Nutrition Examination Survey (KNHANES). The 24-h dietary recall method was used to classify the participants into three groups based on main meal frequency (one, two, or three meals per day) and seven groups based on the type of main meal they skipped. Multivariable logistic regression analysis was conducted to determine the association between main meal frequency and the types of main meals skipped with the odds of MetS and its associated components. Appropriate estimates were accounted for using sampling weights, stratification, and clustering.

The prevalence of MetS in the study population was 33.8%. The average age of the participants was 47.2 years with 42.6% being men, and 57.4% being women. Men who consumed two meals per day had higher odds of MetS than those who consumed three meals per day (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.01-1.33). Women who consumed two meals per day, and skipped breakfast had increased odds of having elevated fasting blood glucose levels (OR 1.18, 95% CI 1.02-1.35), and elevated triglycerides (OR 1.19, 95% CI 1.02-1.39). However, women who skipped dinner had reduced odds of having elevated fasting blood glucose levels (OR 0.74, 95% CI 0.58-0.94).

Our findings suggest that meal frequency and the type of main meal skipped may be associated with MetS and emphasize the importance of consuming breakfast to prevent MetS.

Cardiovascular diseases (CVD) are the major cause of mortality worldwide, whose most prominent risk factor is unhealthy eating habits, such as high fructose intake. Biogenic amines (BAs) perform important functions in the human body. However, the effect of fructose consumption on BA levels is still unclear, as is the association between these and CVD risk factors.

This study aimed to establish the association between BA levels and CVD risk factors in animals that consumed fructose.

Male Wistar rats received standard chow (n=8) or standard chow + fructose in drinking water (30%) (n=8) over a 24-week period. At the end of this period, the nutritional and metabolic syndrome (MS) parameters and plasmatic BA levels were analyzed. A 5% level of significance was adopted.

Fructose consumption led to MS, reduced the levels of tryptophan and 5-hydroxitryptophan, and increased histamine. Tryptophan, histamine, and dopamine showed a correlation with metabolic syndrome parameters.

Fructose consumption alters BAs associated with CVD risk factors.

Recently the complexation-mediated antioxidative and glycaemic control synergism between zinc(II) and caffeic acid was demonstrated in vitro. The present study evaluated the complexation-mediated antidiabetic and antioxidative synergism between zinc(II) and caffeic acid in diabetic rats and the possible underlying mechanisms. Male SD rats were induced with diabetes using 10% fructose and 40 mg/kg bw streptozotocin. The diabetic rats were treated with Zn(II)-caffeic acid complex and its precursors (caffeic acid and zinc acetate) for 4 weeks at predetermined doses. The effect of the treatments on diabetes and oxidative stress was measured. The complex ameliorated diabetic alterations. It reduced polyphagia and polydipsia and recovered weight loss. It increased insulin secretion, insulin sensitivity, hepatic and muscle glycogen, muscle hexokinase activity and Akt phosphorylation, which resulted in improved glucose tolerance and reduced blood glucose in the diabetic rats. The complex concomitantly reduced systemic and tissue lipid peroxidation and increased antioxidant enzymes activity in the diabetic rats. The complex outperformed the antidiabetic and antioxidative action of its precursors and had a broader bioactivity profile. Complexing zinc acetate with caffeic acid improved their ameliorative effect on insulin resistance by ∼24% and 42%, respectively, as well as their anti-hyperglycaemic action by ∼24 - 36% and ∼42 - 47%, respectively, suggesting a complexation-mediated synergism. In some instances, the antidiabetic action of the complex was comparable to metformin, while its antioxidant effect was better than that of metformin. Zinc(II)-caffeic acid complexation may be an alternative approach to improving the efficacy of antidiabetic and antioxidative therapy with minimal adverse or side effects.

Few studies considered the association between snack patterns and metabolic abnormalities. Here we aimed to characterize the major snack patterns among Iranian adults and determine their association with the risk of metabolic syndrome (MetS).

This study was conducted on 1713 MetS-free adults who participated in the third phase of the Tehran Lipid and Glucose Study (TLGS). At baseline, dietary intake of snack was assessed using a validated 168-items food frequency questionnaire, and snack patterns were obtained by principal component analysis (PCA). Adjusted Hazard Ratios (HRs) and 95% confidence intervals (CIs) were calculated for the association of incident MetS with the extracted snack patterns.

PCA identified five major snack patterns, defined as "healthy pattern", "low-fructose pattern", "high-trans pattern", "high-caffeine pattern" and "high-fructose pattern". Participants in the highest tertile of the "high-caffeine pattern" had lower risk of MetS (HR = 0.80, 95% CI = 0.65-0.99, P for trend = 0.032). Other snack patterns have not shown any significant association with MetS incidence.

Our findings suggest that consuming a snack pattern with high loads of caffeine, defined as "High-caffeine pattern" in the present study, could reduce the risk of MetS in healthy adults. Further prospective studies are needed to more fully determine the association between snack patterns and MetS incidence.

Metabolic diseases are often associated with high fructose (HF) consumption. HF has also been found to alter the gut microbiota, which then favors the development of nonalcoholic fatty liver disease. However, the mechanisms underlying of the gut microbiota on this metabolic disturbance are yet to be determined. Thus, in this study, we further explored the effect the gut microbiota concerning the T cells balance in an HF diet mouse model. We fed mice 60% fructose-enriched diet for 12 weeks. At 4 weeks, HF diet did not affect the liver, but it caused injury to the intestine and adipose tissues. After 12 weeks, the lipid droplet aggregation was markedly increased in the liver of HF-fed mice. Further analysis of the gut microbial composition showed that HF decreased the Bacteroidetes/Firmicutes ratio and increased the levels of Blautia, Lachnoclostridium, and Oscillibacter. In addition, HF can increase the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the serum. T helper type 1 cells were significantly increased, and regulatory T(Treg) cells were markedly decreased in the mesenteric lymph nodes of the HF-fed mice. Furthermore, fecal microbiota transplantation alleviates systemic metabolic disorder by maintaining liver and intestinal immune homeostasis. Overall, our data indicated that intestinal structure injury and intestinal inflammation might be early, and liver inflammation and hepatic steatosis may be a subsequent effect following HF diets. Gut microbiota disorders impairing the intestinal barrier function and triggering immune homeostasis imbalance may be an importantly responsible for long-term HF diets induced hepatic steatosis.

Regular consumption of sugar-sweetened beverages has been related to metabolic diseases. Our objective was to identify beverage consumption patterns, nutrient intake, and their possible association with the prevalence of cardiovascular risk factors among Mexican young adults. A cross-sectional survey was conducted. Beverage consumption patterns were obtained by principal components analysis. Logistic regression models were applied to assess the association between the beverage patterns and cardiovascular risk factors. Four beverage patterns were identified. Higher consumption of alcoholic beverages was associated with lower odds for high body fat percent (OR: 0.371; 95% CI: 0.173-0.798), high blood pressure (OR: 0.318; 95% CI: 0.116-0.871), and high glucose (OR: 0.232; 95% CI: 0.061-0.875). Higher consumption of yogurt was associated with lower odds for high glucose (OR: 0.110; 95% CI: 0.22-0.559). In contrast, highest consumption of juice had greater odds for high triglycerides (OR: 1.084; 95% CI: 1.011-4.656). Higher consumption of milk was associated with greater odds for high glucose (OR: 5.304; 95% CI: 1.292-21.773). Beverage consumption habits in Mexican young adults are associated with increased risk factors for cardiovascular disease. Therefore, intervening during young adulthood should be considered in order to improve current health and prevent cardiovascular mortality in later decades.

Fructose (C₆H₁₂O₆) is acutely obesogenic and is a risk factor for hypertension, cardiovascular disease, and nonalcoholic fatty liver disease. However, the possible long-lasting effects of early-life fructose consumption have not been studied. We tested for effects of early-life fructose and/or wheel access (voluntary exercise) in a line of selectively bred High Runner (HR) mice and a non-selected Control (C) line. Exposures began at weaning and continued for 3 weeks to sexual maturity, followed by a 23-week "washout" period (equivalent to ∼17 human years). Fructose increased total caloric intake, body mass, and body fat during juvenile exposure, but had no effect on juvenile wheel running and no important lasting effects on adult physical activity or body weight/composition. Interestingly, adult maximal aerobic capacity (VO₂max) was reduced in mice that had early-life fructose and wheel access. Consistent with previous studies, early-life exercise promoted adult wheel running. In a 3-way interaction, C mice that had early-life fructose and no wheel access gained body mass in response to 2 weeks of adult wheel access, while all other groups lost mass. Overall, we found some long-lasting positive effects of early-life exercise, but minimal effects of early-life fructose, regardless of the mouse line.