Search Results (228)

A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)—also known as GlucoRegulate—induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose and low-grade inflammation in overweight and obese subjects in a clinical trial. The aim of this study was to explore, for the first time, health-beneficial gene expression other than Glo1 induced by tRES+HESP in human endothelial cells and fibroblasts in primary culture and HepG2 hepatoma cell line and activity of cis-resveratrol (cRES) as a Glo1 inducer. We measured antioxidant response element-linked gene expression in these cells in response to 5 µM tRES+HESP by the NanoString method. tRES+HESP increases gene expression linked to the prevention of dicarbonyl stress, lipid peroxidation, oxidative stress, proteotoxicity and hyperglycemia-linked glycolytic overload. Downstream benefits were improved regulation of glucose and lipid metabolism and decreased inflammation, extracellular matrix remodeling and senescence markers. The median effective concentration of tRES was ninefold lower than cRES in the Glo1 inducer luciferase reporter assay. The GlucoRegulate supplement provides a new treatment option for the prevention of type 2 diabetes and metabolic dysfunction–associated steatotic liver disease and supports healthy aging. Full article

Background/Objectives: Diatomaceous earth (DE), a natural substance rich in amorphous silica and recognized as a food additive, is gaining attention as a dietary silicon supplement. However, its bioavailability and impact on lipid digestion and absorption remain poorly characterized. This study aimed to investigate silicon bioavailability after short-term DE supplementation and its effects on postprandial glycemia and triglyceridemia, the expression of lipid metabolism-related proteins, and the modulation of the intestinal mucosal barrier. Methods: Female Wistar rats received daily oral supplementation of DE (equivalent to 2 or 4 mg silicon/kg body weight) for one week. Silicon digestibility, excretion, and hepatic accumulation were quantified. Postprandial glycemia and triglyceridemia were monitored. Lipid profile was analyzed by HPSEC in gastric and intestinal contents. Jejunal morphology and mucin-secreting cells were assessed histologically. Lipid metabolism markers were evaluated by immunohistochemistry and Western blot in both intestinal and hepatic tissues. Results: DE supplementation enhanced silicon absorption and increased hepatic levels. Fecal output and moisture content were also elevated, especially at the higher dose. DE significantly reduced postprandial triglyceridemia and consequently increased luminal triglyceride retention. These changes were associated with decreased jejunal levels of IFABP, ACAT2, and MTP, as well as reduced hepatic levels of MTP and LDLr, alongside increased levels of ABCG5/G8 and LXRα/β, indicating a partial blockage of lipid absorption and enhanced cholesterol efflux. The effects on the intestinal barrier were evidenced by villi shortening and an increase in mucin-producing cells. Conclusion: Food-grade DE is a bioavailable source of silicon with hypolipidemic potential, mainly by reducing intestinal lipid absorption. This is supported by lower postprandial triglycerides, increased luminal lipid retention, and decreased expression of lipid transport proteins. The study in healthy female rats underscores the importance of sex-specific responses and supports DE as a dietary strategy to improve lipid metabolism. Full article

Background/Objectives: Asprosin is the endogenous ligand of the olfactory Olfr734 receptor linked to MASLD and glucose metabolism. Despite the involvement of asprosin in these processes, little has been published on the specific role of Olfr734 in liver function. The aim of this work is therefore to study the specific role of the olfactory Olfr734 receptor in MASLD and glucose metabolism. Methods: To achieve this objective, we performed a genetic inhibition specifically to inhibit Olfr734 in the livers of male mice. We then studied the progression of MASLD in DIO mice. In addition, we studied the glucose metabolism in hypoglycemia states and postprandial glucose production in standard diet-fed mice. Finally, analyses of liver biopsies from patients with obesity and with or without T2DM were conducted. Results: We found that hepatic Olfr734 levels vary according to changes in nutritional status and its knockdown effect in the liver is to increase the hepatic lipid content in DIO mice. Our results also showed that OLFR734 expression is involved in the adaptive response in terms of glucose production to nutrient availability. Finally, the hepatic human Olfr734 ortholog named OR4M1 has been observed to be at significantly higher levels in male patients with T2DM. Conclusions: This study increases understanding of the mechanisms by which the modulation of Olfr734 expression affects liver function. Full article

Postprandial dysmetabolism, which refers to the impaired regulation of glucose and lipid levels after meals, is recognized as an independent risk factor for cardiovascular diseases (CVDs). Diets rich in polyphenols have demonstrated potential in improving postprandial hyperglycemia and hyperlipidemia. This study investigates the effects of olive leaf polyphenols on postprandial metabolic outcomes following a high-fat and high-carbohydrate meal. A total of 36 healthy adults participated in a three-arm randomized crossover trial. They ingested either a biscuit made from olive leaf powder (OLB), olive leaf tea (OLT), or a placebo meal (CTRL) to assess the impact of olive leaf polyphenols on postprandial glycemia, lipid levels, platelet aggregation factor (PAF), and plasma antioxidant status (TAC). Although no statistically significant differences were observed in the primary biomarkers, including glucose and lipid profiles, a delayed insulin response was noted in the interventions involving olive leaf. These findings suggest that while acute olive leaf supplementation did not significantly alter postprandial glycemia or lipidemia, it may subtly influence insulin kinetics. Further research is needed to explore the long-term effects of olive leaf polyphenols on metabolic health, especially in populations at risk for CVDs. Full article

Bioactive compounds have shown significant potential in the management of obesity and metabolic syndrome (MetS). This study investigates the effects of antioxidant lipids (ALω-3), synthetized through enzymatic acidolysis using non-specific lipase B from Candida antarctica under supercritical CO₂ conditions. These lipids were derived from a concentrate of rainbow trout (Oncorhynchus mykiss) belly oil, rich in long-chain polyunsaturated omega-3 fatty acids (LCPUFAn-3), and cold-pressed maqui seed oil (MO, Aristotelia chilensis (Mol.) Stuntz). Their effects were then evaluated in a murine high-fat diet (HFD) model. The fatty acid profile, tocopherol and tocotrienol content, and thin-layer chromatography of ALω-3 were analyzed. After 8 weeks on an HFD, male C57BL/6 mice were divided into four groups and switched to a control diet (CD) with the following supplements for 3 weeks: Glycerol (G), commercial marine Omega-3 (CMω-3), a mixture of LCPUFAn-3 concentrate + MO (Mω-3), or ALω-3. The total body and organ weights, serum markers, and liver and visceral fat pro-inflammatory marker expression levels were assessed. ALω-3 contained 13.4% oleic, 33.9% linoleic, 6.3% α-linolenic, 10.7% eicosapentaenoic, and 16.2% docosahexaenoic fatty acids. The β, γ, δ-tocopherol, and β, γ-tocotrienol values were 22.9 ± 1.4, 24.9 ± 0.2, 6.8 ± 0.7, 22.9 ± 1.7, and 22.4 ± 4.7 mg·kg⁻¹, respectively, with α-tocopherol detected in traces. ALω-3 supplementation increased serum Trolox equivalent capacity, significantly reduced serum GPT levels (p < 0.01), and enhanced postprandial glucose tolerance (p < 0.001), although it did not alter insulin resistance (HOMA-IR). These findings indicate ALω-3′s potential for mitigating the glucose intolerance, liver damage, and oxidative stress associated with obesity and MetS, highlighting the need for additional research to explore its potential health benefits. Full article

Despite advances in technology, the overall management of type 1 diabetes mellitus (T1DM) remains suboptimal. The idea of restricting carbohydrate intake to decrease glycemic spikes and insulin requirements has been revisited in recent years. After impressive results in the fields of type 2 diabetes (T2DM) and epilepsy, low-carbohydrate (LCD) and ketogenic (KD) diets have gained renewed interest as a possible treatment option for T1DM. In this narrative review, we discuss the available data regarding LCDs and KDs in both the adult and pediatric populations. Research data is still scarce, as most studies are short-term and show considerable heterogeneity in dietary composition and patient outcomes. In general, carbohydrate restriction enhances glycemic control by reducing postprandial glucose excursions, improving time-in-range, and lowering HbA1c, with conflicting effects on other parameters such as lipid profile and body weight. Adverse effects such as hypoglycemia and diabetic ketoacidosis are rarely reported, although some concerns have been raised regarding growth in children. The correct implementation of these diets requires a multidisciplinary approach by highly specialized healthcare professionals, who will address the medical, social, and psychological concerns that a restrictive diet entails. Large-scale and long-term studies are needed to provide more robust data before carbohydrate restriction can be widely applied to patients with T1DM. Full article

Background/Objectives: Cyclodextrins (CDs) have garnered increasing attention in pharmaceutical research due to their ability to enhance drug solubility, bioavailability, and therapeutic efficacy. Meanwhile, the gut microbiota, a key regulator of human health, has emerged as an important target in evaluating the safety and broader implications of pharmaceutical excipients. This review aims to synthesize current knowledge regarding the effects of CDs on the composition and function of the gut microbiota. Methods: A literature search following PRISMA guidelines was conducted in PubMed, ScienceDirect, and Google Scholar to identify studies on cyclodextrins and their interactions with gut microbiota. Results: Cyclodextrins, particularly α-, β-, and γ-CDs, demonstrated the capacity to modulate gut microbiota composition, promoting the growth of beneficial bacteria such as Bifidobacterium and Akkermansia. Supplementation with CDs was also associated with an increased production of short-chain fatty acids (SCFAs), which are essential for maintaining intestinal homeostasis and metabolic health. Moreover, CDs exhibited potential in lowering lipid levels and improving postprandial glycemic control without enhancing insulin secretion. Although generally recognized as safe, the toxicological profile of CDs varies depending on their type, dosage, and route of administration. Conclusions: Cyclodextrins hold considerable promise not only as pharmaceutical excipients but also as modulators of gut microbial communities, suggesting a dual therapeutic and prebiotic role. Future studies integrating metagenomic and metabolomic approaches are necessary to further elucidate the molecular mechanisms underlying CD–microbiota interactions and to optimize their application in enhancing drug delivery efficiency and promoting intestinal health. Full article

Zinc-alpha2-glycoprotein (ZAG) is a soluble glycoprotein primarily produced in adipocytes and the liver, with key roles in lipid metabolism, including lipolysis and the browning of adipose tissue. Despite extensive studies on its role in rodents, the relationship between ZAG and insulin in humans remains unclear. Given the emerging interest in ZAG’s involvement in metabolic diseases such as metabolic-dysfunction-associated steatotic liver disease, this study aimed to investigate the acute effects of insulin on ZAG levels both in vivo and in vitro. We recruited 24 healthy, individuals who were non-obese and assessed the impact of oral glucose overload, a standardized liquid nutritional supplement, and intravenous glucagon on circulating ZAG levels. In parallel, we explored the effects of insulin on ZAG production in cultured HepG2 cells. Our findings revealed a consistent acute reduction in serum ZAG levels following all in vivo tests, coinciding with increased insulin levels. In vitro, insulin rapidly downregulated ZAG protein and mRNA levels in HepG2 cells, with significant reductions observed within 15 min, followed by partial recovery after 2 h. These results suggest a potential acute inhibitory effect of insulin on ZAG production, supporting its role in promoting energy storage by suppressing lipolysis postprandially. This study provides new insights into the complex interplay between insulin and ZAG in regulating energy balance and highlights the potential of ZAG as a therapeutic target in metabolic diseases. Full article

Olive oil (OO) has longstanding significance in human history, particularly in the Mediterranean region, where it has been a cornerstone of diet, economy, and culture. This history adds to modern evidence-based knowledge. Background: The Mediterranean diet (MD), rich in plant-based foods and OO, has been extensively associated with improved cardiometabolic and cognitive health. Recent interest has emerged in understanding how intermittent fasting protocols may enhance these effects. Still, the quality of OO does not only lie in the extraction process; it is also dependent on the tree variety, the soil, and the agricultural practices, ending with the way in which the finished product is stored and consumed. Objectives: This review explores the synergistic potential between OO consumption and intermittent fasting, focusing on their combined impact on metabolic health, oxidative stress, and inflammatory pathways. Methods: A literature search was conducted using multiple databases to identify studies addressing the health effects of OO, fasting, and the MD. Both human and relevant preclinical studies were considered, with emphasis on those evaluating inflammatory markers, lipid metabolism, insulin sensitivity, and neuroprotective mechanisms. Results: Evidence suggests that the bioactive compounds in EVOO may potentiate the benefits of fasting by enhancing antioxidant capacity, reducing postprandial inflammation, and modulating gene expression related to cellular metabolism. Combined, these factors may support improved insulin sensitivity, reduced oxidative damage, and delayed onset of age-related diseases. Conclusions: Understanding the integrative role of OO and fasting within the MD framework could offer valuable insights for nutritional strategies aimed at preventing metabolic syndrome, type 2 diabetes, and neurodegeneration. These findings also support the need for future clinical trials exploring the timing, dosage, and dietary context in which these interventions are most effective. Full article

Background and Objectives: Prediabetes (PD) is characterized by impaired glucose metabolism and is associated with an elevated risk of type 2 diabetes and cardiovascular diseases. This study aimed to investigate the effects of an 8-week core exercise intervention on glycemic control, lipid profiles, insulin sensitivity, body composition, and physical performance in prediabetic women. Materials and Methods: Eighteen prediabetic women aged 20–55 years were randomly allocated to either a core exercise group (n = 9) or a control group (n = 9). The intervention group completed 24 supervised core exercise sessions over 8 weeks, whereas the control group remained sedentary. Pre- and post-intervention evaluations included anthropometric measurements, flexibility and strength tests, fasting and postprandial glucose levels, HbA1c, insulin, HOMA-IR, lipid profiles, and serum iron levels. Non-parametric tests were used for statistical analysis, and a Principal Component Analysis (PCA) and hierarchical clustering were conducted to explore multidimensional metabolic changes. Results: Core exercise significantly improved the body weight, BMI, fat percentage, and circumferences (shoulder, chest, and hip), along with an enhanced flexibility and back-leg strength (p < 0.05). Glycemic indices (FBG, PBG, and HbA1c), insulin, and HOMA-IR levels were significantly reduced, while serum iron and HDL-C increased (p < 0.05). Lipid markers, including the TG, LDL-C, CHOL, and TG/HDL-C ratio, showed significant improvements. The PCA and cluster analyses identified three clusters reflecting metabolic risk, body composition, and protective factors. Conclusions: This study demonstrates that an 8-week structured core exercise program significantly improves glycemic control, lipid profiles, insulin sensitivity, and body composition in women with prediabetes. Multivariate analyses (PCA and hierarchical clustering) corroborate a metabolic shift towards a reduced insulin resistance and a more favorable cardiometabolic profile, supporting core training as a viable, evidence-based non-pharmacological intervention to mitigate metabolic risk. Full article

Background: Though evidence is limited, animal products like pork sausages and cheese may affect satiety differently due to their distinct protein, fat, and calcium content. This study therefore compared their acute effects on breakfast using appetite-related markers. Methods: A total of 11 women and 13 men, with a mean age of 23.0 ± 2.6 years and mean BMI of 24.5 ± 2.6 kg/m², participated in this crossover design study. Concentrations of active ghrelin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), insulin, glucose, leptin, and blood lipids were measured. Subjective feelings of appetite using visual analogue scales were analyzed (0–4 h) as a response to two test breakfasts meals with a similar energy and macronutrient content. Appetite feelings and energy intake from an ad libitum buffet lunch were subsequently measured. Data were analyzed using two different ANOVA methods. Results: The pork sausage breakfast was characterized by an earlier triglyceride (TG) peak than the cheese. A slower TG clearance was seen with the cheese breakfast. Ghrelin suppression was longer in the pork sausage breakfast. Active GLP-1 concentration was higher following the cheese breakfast and active GIP declined slower. The two ANOVA methods disagreed regarding the insulin effect. Subjective feelings of hunger before buffet and ad libitum energy intake were higher in males (791 ± 64 kcal) compared with females (344 ± 32 kcal), but did not differ between breakfast types. Conclusions: Acute consumption of pork and cheese of the same energy, fat, and protein content provided detectable differences in appetite-related hormones and lipid responses. Appetite and lipid metabolism were affected by the major differentiators of the test meals, namely calcium, fatty acids and amino acids compositions. Full article

Sustainable health approaches promote functional food alternatives that support metabolic well-being while reducing reliance on added sugars and artificial sweeteners. Monk fruit extract (MFE), a natural, non-caloric sweetener, is gaining interest for its potential metabolic benefits, but its effects and regulatory status require further evaluation. Objective: This PRISMA-guided systematic review synthesizes findings from randomized controlled trials (RCTs) assessing the impact of MFE on metabolic health, lipid profiles, inflammation, and regulatory considerations. Methods: The literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library, covering studies published between 2015 and 2025. Inclusion criteria were human RCTs evaluating MFE’s metabolic effects, while animal studies, reviews, and mixed-intervention trials were excluded. Study quality was assessed using the Cochrane risk of bias tool and the Jadad scale. Results: Five randomized controlled trials met the inclusion criteria, demonstrating that monk fruit extract (MFE) reduces postprandial glucose levels by 10–18% and insulin responses by 12–22%. No severe adverse effects were observed. Regulatory analysis indicated that MFE is approved for use in the United States and China, while its status remains under review in the European Union. Conclusions: MFE shows potential as a functional food ingredient for metabolic health. However, long-term clinical trials and a harmonized regulatory framework must confirm its safety and efficacy within sustainable health strategies Full article

Type 2 diabetes is characterized by insulin resistance, which contributes to dysregulated glucose and lipid metabolism and is associated with chronic inflammation. While previous studies have examined the effects of myricitrin in streptozotocin-induced diabetic models, its impact on the db/db mouse, a model that better reflects insulin resistance-associated metabolic disturbances, remains unclear. In this study, mice were divided into three groups (db/+, db/db, and db/db + 0.02% myricitrin) and were fed their respective diets for five weeks. Myricitrin supplementation reduced fat mass, adipocyte size, and plasma leptin levels, which were elevated in db/db mice. Although myricitrin did not affect fasting blood glucose levels, it lowered plasma insulin, hemoglobin A1c, postprandial glucose levels, and the homeostasis model assessment of insulin resistance, suggesting improvements in insulin sensitivity and glucose homeostasis. Enhanced pancreatic insulin expression, along with reduced hepatic gluconeogenic enzyme activities and mRNA expression, contributed to the improved glucose homeostasis observed in myricitrin-supplemented mice. Additionally, myricitrin reduced hepatic triglyceride levels and lipid droplet accumulation by inhibiting hepatic fatty acid synthase activity. It also decreased plasma inflammatory marker levels and their mRNA expression in adipose tissue. These findings suggest that myricitrin may be a promising therapeutic candidate for type 2 diabetes. Full article

Obesity and type 2 diabetes mellitus (T2DM) are major health concerns worldwide, often managed with treatments that have significant limitations and side effects. This study examines the potential of sodium alginates, extracted from Ecklonia radiata and Sargassum elegans, to inhibit digestive enzymes involved in managing these conditions. We chemically characterized the sodium alginates and confirmed their structural integrity using FTIR, NMR, and TGA. The focus was on evaluating their ability to inhibit key digestive enzymes relevant to T2DM (α-amylase, α-glucosidase, sucrase, maltase) and obesity (pancreatic lipase). Enzyme inhibition assays revealed that these sodium alginates moderately inhibit α-glucosidase, maltase, and lipase by up to 43%, while showing limited effects on sucrase and α-amylase. In addition, the sodium alginates did not affect glucose uptake in human colorectal cells (HCT116), indicating they do not impact cellular glucose absorption. In summary, while the observed enzyme inhibition was moderate, the targeted inhibition of α-glucosidase, maltase, and lipase suggests that sodium alginates could be beneficial for managing postprandial hyperglycemia and lipid absorption in the context of T2DM and obesity. Full article

Background/Objectives: Yacon syrup (Smallanthus sonchifolius) has gained attention due to its high concentration of fructooligosaccharides (FOSs) and associated health benefits. This systematic review aimed to evaluate the effects of yacon syrup on metabolic parameters and intestinal health in humans over the last decade. Methods: Following PRISMA guidelines, we conducted a systematic search in databases, including Medline (PubMed), Science Direct, Embase, Scopus, and SciELO, up to October 2024. Inclusion criteria focused on clinical trials examining the impact of yacon syrup on glycemic control, lipid profile, insulin sensitivity, appetite regulation, and gut microbiota in healthy, overweight, or obese individuals. Seven studies met the inclusion criteria, encompassing 161 participants from diverse populations. Results: Yacon syrup supplementation demonstrated significant reductions in fasting insulin, HOMA-IR, and LDL cholesterol, alongside improvements in satiety and intestinal transit time. Acute supplementation with yacon syrup had inconsistent results for postprandial glycemia and insulin levels, probably due to prior individual gut microbiota composition. Longer interventions with yacon syrup were associated with enhanced microbiota modulation and appetite regulation, particularly in women. Mild gastrointestinal discomfort was reported, but with the continued use of yacon syrup, the symptoms decreased. Yacon syrup presents promising health benefits, including improved insulin sensitivity, weight management, and gut health. However, further research is needed to establish optimal dosing and long-term safety. Conclusions: This review highlights the potential of yacon syrup as a functional supplement for metabolic and gastrointestinal health. Full article