Improve Glucose Metabolism Research Articles

Role of transforming growth factor-β1 in regulating adipocyte progenitors

Adipose tissue (AT) metabolism involves coordinating various cells and cellular processes to regulate energy storage, release, and overall metabolic homeostasis. Therein, macrophage and its cytokine are important in controlling tissue homeostasis. Among cytokines, the role of transforming growth factor-β1 (Tgf-β1), a cytokine abundantly expressed in CD206+ M2-like macrophage and correlated with the expansion of AT and fibrosis, in AT metabolism, remains unknown. We used CD206CreERT2; Tgf-β1f/f mouse model in which the Tgf-β1 gene was conditionally deleted in CD206+ M2-like macrophages followed by tamoxifen administration, to investigate the role of the Tgf-β1 gene in glucose and insulin metabolism. Our data demonstrated that lack of CD206+ M2-like macrophages derived Tgf-β1 gene improved glucose metabolism and insulin sensitivity by enhancing adipogenesis via hyperplasia. The Tgf-β1 gene, specifically from CD206+ M2-like macrophages, deletion stimulated APs’ proliferation and differentiation, leading to the generation of smaller mature adipocytes, therefore enhancing insulin sensitivity and improving glucose metabolism under normal chow conditions. Our study brings a new perspective that Tgf-β1 gene deletion specific from CD206+ M2-like macrophage promotes adipocyte hyperplasia, improving glucose homeostasis and insulin sensitivity in the lean state.

Comprehensive Analysis of Fecal Microbiome and Metabolomics Uncovered dl-Norvaline-Ameliorated Obesity-Associated Disorders in High-Fat Diet-Fed Obese Mice by Targeting the Gut Microbiota.

Norvaline is a nonproteinogenic amino acid and an important food ingredient supplement for healthy food. In this study, dl-norvaline administration reduced body weight by more than 40% and improved glucose metabolism and energy metabolism in obese mice induced by a high-fat diet (HFD). Combination analysis of microbiome and metabolomics showed that dl-norvaline supplementation regulated gut bacteria structure, such as increasing beneficial bacteria (Mollicutes_RF39, Ruminococcaceae, Bacteroidaceae, Rikenellaceae, Lactobacillaceae, Clostridiaceae_1, uncultured_bacterium_f_Muribaculaceae, and Rikenellaceae_RC9_gut_group) and decreasing harmful bacteria (Fusobacteriia, Desulfovibrionales, Enterobacteriaceae, Burkholderiaceae, Helicobacteraceae, and Veillonellaceae) and modulated the metabolites involved in arachidonic acid metabolism, thus further promoting short-chain fatty acid production and improving gut barrier, thereby inflammatory responses and oxidative stress were ameliorated. In addition, the pseudogerm-free mouse model verified that dl-norvaline ameliorated obesity-associated disorders in HFD-fed obese mice by targeting gut microbiota. These results clarified that dl-norvaline may be promising for developing and innovating potential functional food products.

Environmental enrichment normalizes metabolic function in the murine model of Prader-Willi syndrome Magel2-null mice.

Prader-Willi syndrome (PWS) is a rare genetic disease that causes developmental delays, intellectual impairment, constant hunger, obesity, endocrine dysfunction, and various behavioral and neuropsychiatric abnormalities. Standard care of PWS is limited to strict supervision of food intake and growth hormone therapy, highlighting the unmet need for new therapeutic strategies. Environmental enrichment (EE), a housing environment providing physical, social, and cognitive stimulations, exerts broad benefits on mental and physical health. Here, we assessed the metabolic and behavioral effects of EE in the Magel2-null mouse model of PWS. EE initiated after the occurrence of metabolic abnormality was sufficient to normalize body weight and body composition, reverse hyperleptinemia, and improve glucose metabolism in the male Magel2-null mice. These metabolic improvements induced by EE were comparable to those achieved by a hypothalamic brain-derived neurotrophic factor (BDNF) gene therapy although the underlying mechanisms remain to be determined. These data suggest biobehavioral interventions such as EE could be effective in the treatment of PWS-related metabolic abnormalities.

The Glucose-Lowering Effect of Mesembryanthemum crystallinum and D-Pinitol: Studies on Insulin Secretion in INS-1 Cells and the Reduction of Blood Glucose in Diabetic Rats.

Background: Ice plant (Mesembryanthemum crystallinum) is a vegetable with various therapeutic uses, one of which is its ability to prevent diabetes. The present study examined the insulin secretion effect related to the mechanism of action of ice plant extract (IPE) and its active compound D-pinitol in a rat insulin-secreting β-cell line, INS-1, as well as in diabetic rats. Methods: The glucose-stimulated insulin secretion (GSIS) test and Western blotting were used to measure GSIS. The glucose-stimulated index (GSI) and expression levels of insulin-related pathway factors, including insulin receptor substrate-2 (IRS-2), phosphoinositide 3-kinase (PI3K), Akt, and pancreatic and duodenal homeobox-1 (PDX-1), were measured in INS-1 cells. Results: The results showed that the GSI values were found to be 8.17 ± 0.22 and 12.21 ± 0.22 for IPE (25 μg/mL) and D-pinitol (100 μM), respectively. GSI values increased statistically significantly. In addition, IPE and D-pinitol upregulated the expression of insulin-related pathway factors. These findings indicate that insulin secretion was significantly stimulated by IPE and D-pinitol in the INS-1 cells, partly by upregulating the expression of IRS-2, PI3K, Akt, and PDX-1. Additionally, IPE administration significantly reduced excessive weight gain and improved glucose tolerance by decreasing the OGTT-AUC. It demonstrated liver-function-improving and lipid-lowering effects by reducing serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), triglyceride levels, and total cholesterol levels. Mechanistically, IPE enhances insulin signaling by increasing insulin receptor substrate 1 (IRS-1) phosphorylation and improving glucose metabolism and insulin sensitivity. Conclusions: These results offer important new information on the potential of D-pinitol and IPE as functional foods for improving insulin secretion and managing metabolic dysregulation associated with diabetes.

The effect of heating therapy on the blood profile of white rats (Rattus norvegicus)

A decrease in the number of erythrocytes and hemoglobin levels was one of the complications of diabetes mellitus (DM). One of the treatments for DM patients used Heating Therapy (HT). Heating Therapy is a treatment in the form of heat exposure which can cause increased expression of heat shock protein (HSP), improve glucose metabolism, insulin sensitivity and improve insulin signaling. The aim of this research was to determine the effect of heating therapy on the blood profile of mice. This research used a Complete Random Plan, which had five treatments and six replications. Rats without treatment (K-), diabetic rats (K+), rats given HT at 37°C for 10 minutes (P1), HT at 37°C for 20 minutes (P2) and HT at 37°C for 30 minutes (P3)). Heating Therapy was given every day for 3 weeks. One-way ANOVA test was used to analyze research data. If there was a significant difference (P <0.05), then proceed with the Duncan post-hoc test. The results showed that the control group and the treated group of mice given HT had significant differences (P <0.05). By giving HT at a temperature of 37°C for 10 minutes was effective in increasing hemoglobin levels and improving the number of platelet cells in diabetic mice.

Pediococcus acidilactici CECT 9879 (pA1c®) and heat inactivated pA1c® (pA1c® HI) ameliorate gestational diabetes mellitus in mice.

Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and is known to be associated with an increased risk of postpartum metabolic disease. Based on the important role that the intestinal microbiota plays in blood glucose regulation and insulin sensitivity, supplementation of probiotic and postbiotic strains could improve glucose metabolism and tolerance in GDM. 56 4-week-old female C57BL/6J-mice were divided into 4 groups (n=14 animals/group): control (CNT), high-fat/high-sucrose (HFS), pA1c® alive (pA1c®) and heat-inactivated pA1c® (pA1c®HI). Serum biochemical parameters were analyzed, gene expression analyses were conducted, and fecal microbiota composition was evaluated by shot-gun sequencing. pA1c®- and pA1c® HI-supplemented groups presented reduced fasting blood glucose levels and reduced insulin resistance during gestation and exhibited lower visceral adiposity and increased muscle tissue, together with an improvement in intrahepatic TGs content and ALT levels. Liver gene expression analyses demonstrated that pA1c® and pA1c® HI activities were mediated by modulation of the insulin receptor, but also by an overexpression of beta-oxidation genes, and downregulation of fatty acid biosynthesis genes. Shot-gun metagenomics demonstrated that Pediococcus acidilactici was detected in the feces of all the pA1c® and pA1c® HI-group after the supplementation period (75% of the microbial profile was Pediococcus acidilactici) in only nine weeks of supplementation, and modulated gut microbiota composition. These results may be considered as future perspectives for the development of preventive, even therapeutic options for GDM based on hyperglycemia reduction, blood glucose regulation, hepatic steatosis attenuation and insulin resistance alleviation.

Complexation of starch and konjac glucomannan during screw extrusion exhibits obesity-reducing effects by modulating the intestinal microbiome and its metabolites.

Dietary interventions have been shown to improve gut health by altering the gut flora, preventing obesity, and mitigating inflammatory disorders. This study investigated the benefits of a rice starch-konjac glucomannan (ERS-KGM) complex, produced via screw extrusion, for gut health and obesity prevention. Analyzed through in vitro starch digestion, scanning electron microscopy, and structural analysis, the ERS-KGM complex exhibited a notable increase in resistant starch content due to its well-ordered structure. When administered to mice on a high-fat diet for 8 weeks, the ERS-KGM complex significantly reduced body weight, white adipose tissue mass, adipocyte size, and food intake while increasing water consumption. It also improved glucose metabolism, insulin sensitivity, and lipid profiles by lowering serum triglycerides and total glycerol content. Enhanced metabolic biomarkers and enzyme activities were observed, specifically involving glycerophospholipid metabolism. It decreased the activities of aldehyde dehydrogenase, lactate dehydrogenase, and amino acid transaminase while increasing antioxidant enzymes like glutathione peroxidase and superoxide dismutase. Additionally, it elevated glycogen and positively altered gut microbiota by enriching Firmicutes, Desulfobacterota, and Bifidobacterium. This change enhanced the ability to degrade specific compounds and elevated the concentrations of short-chain fatty acids in feces. These findings suggest that the ERS-KGM complex could serve as a dietary supplement for obesity prevention.

Akkermansia muciniphila inhibits jejunal lipid absorption and regulates jejunal core bacteria.

Insufficiency of Akkermansia muciniphila (Akk) has been implicated in the pathogenesis of metabolic diseases, and administration or restoration of Akk has ameliorated these disorders. Recently, Pasteurized Akk (PA-Akk) has been approved as a functional food. However, the impact of Akk on lipid absorption in the proximal intestine, which is directly exposed to orally administered Akk, remains largely unexplored. In this study, we orally administered Akk and PA-Akk to mice and investigated the subsequent lipid absorption. Long-term administration of Akk resulted in reduced lipid deposits in the liver and adipocytes, along with improved glucose metabolism. This was primarily attributed to a reduction in lipid absorption by epithelial cells in the proximal jejunum. Mechanistically, Akk activated AMP-activated protein kinase (AMPK) and directly inhibit lipids absorption in both mouse and human jejunal epithelial cells. Furthermore, we demonstrated that Akk treatment, but not PA-Akk treatment, promotes the abundance of genera that are highly abundant in the normal jejunum and belong to the phylum Firmicutes. Thus, our study concludes that oral administration of Akk provides beneficial effects on metabolism, partially through inhibiting jejunal lipid absorption and promoting the abundance of core jejunal microbes.

Sex-specific differences in insulin response and substrate oxidation after repeated, brief whole-body immersion in 45°C water: A prospective, interventional study.

Prolonged heat exposure is suggested to improve glucose metabolism and fat oxidation, but no studies have addressed whether brief heat stimuli represent a viable, time-efficient, alternative approach. Consequently, we examined the ability of brief stimuli evoked by 45°C water to improve glucose tolerance, insulin sensitivity, and fat oxidation in young, non-obese, males and females. Twenty-four participants completed fourteen 5-min sessions involving whole body passive heating in 45°C water. Changes in resting catecholamines, cytokines, substrate oxidation, resting energy expenditure, glucose tolerance, and insulin release in response to an oral glucose tolerance test, were assessed before and 24-h after intervention, and 1 month after the end of the intervention. The results showed that repeated short-duration heat intervention had no significant effects on epinephrine, norepinephrine, interleukin-6, and tumor necrosis factor alpha production in both sexes. Glucose area under the curve (AUC) was not affected. However, females had a lower insulin AUC and improved insulin sensitivity as indicated by a decrease in homeostatic model assessment for insulin resistance, and an increase in the quantitative insulin sensitivity check index and the Matsuda insulin sensitivity index values one month after the end of the heat intervention. No effect was observed in resting energy expenditure, but carbohydrate oxidation per kilogram increased in females, and this substrate oxidation change was maintained after one month. In conclusion, fourteen sessions of brief 5-min whole-body immersion in 45°C water produced an improvement in insulin sensitivity and increased reliance on carbohydrate oxidation in females.

Improvement of glucose metabolism disorder by wheat dietary fibre depended on the intake mode and regulated through TLRs/NF-κB/TNF pathway in db/db mice

ABSTRACT To study the effect of wheat dietary fibre (WDF) on glucose metabolism disorder and its mechanisms, 6-week-old db/db mice were given WDF by adding to diet or oral-gavage. The results showed that WDF by oral-gavage instead of adding to the feed can significantly reduce blood glucose levels. The levels of insulin and HOMA-IR were both decreased in the serum of WDF-gavaged mice as well as several inflammatory cytokines including TNF-α, IL-6 and IL-1β. WDF intake by gavage could better regulate the intestinal flora, thus inhibiting diabetes. The relative expressions of genes and proteins including TLR, P65, P50 and TNF-α were all significantly decreased by oral-gavaged WDF. Moreover, the ratio of phosphorylated p65 to total p65 was significantly decreased. In conclusion, ingestion of WDF by gavage can effectively improve glucose metabolism disorder in db/db mice by improving intestinal microbiota and regulating the TLRs/NF-κB/TNF pathway.

Pumpkin Soluble Dietary Fiber instead of Insoluble One Ameliorates Hyperglycemia via the Gut Microbiota-Gut-Liver Axis in db/db Mice.

Pumpkin extract has been shown to alleviate hyperglycemic symptoms by improving glucose metabolism disorders. However, the specific active components responsible for its hypoglycemic effects and the underlying molecular mechanisms remain unclear. In this study, db/db mice underwent a 4-week dietary intervention with two pumpkin flours (PF1 and PF2), total dietary fiber (TDF), soluble dietary fiber (SDF), and insoluble dietary fiber (IDF), with acarbose serving as a positive control. Our results revealed that pumpkin components significantly altered the gut microbiota, characterized by a reduction in diabetes-related bacteria and an increase in short-chain fatty acid (SCFA)-producing bacteria, including Bacteroides, Akkermansia, and Lachnospiraceae_NK4A136 group. Additionally, pumpkin components significantly increased fecal SCFA levels and upregulated the expression of SCFA receptor GPR43, potentially promoting GLP-1 secretion. Notably, pumpkin components significantly reduced fasting blood glucose and serum insulin levels and inhibited gluconeogenesis. This effect may be ascribed to the inhibition of the cAMP/PKA/CREB signaling pathway coupled with the activation of the PI3K/AKT signaling pathway. Our research indicated that pumpkin flour and dietary fiber alleviated hyperglycemia through the gut-liver axis, with SDF contributing the most to the hypoglycemic effect. These findings suggest that pumpkin components may serve as an adjunct nutritional intervention to ameliorate hyperglycemia.

Hovenia dulcis (Guaizao) polysaccharide ameliorates hyperglycemia through multiple signaling pathways in rats with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) poses a significant threat to human health, with its incidence and mortality rates increasing annually. This study investigated the hypoglycemic effects and underlying mechanisms of pure Hovenia dulcis (Guaizao) polysaccharide (HDPs-2A) in rats subjected to a high-fat and high-sugar diet combined with streptozotocin-induced T2DM. Oral administration of HDPs-2A resulted in significant increases in body weight and liver glycogen levels compared to untreated controls. Moreover, a reduction in fasting blood glucose levels, alleviation of hyperinsulinemia, enhanced glucose tolerance, and improved insulin resistance were observed in the HDPs-2A-treated group. HDPs-2A also effectively reversed diabetes-induced dyslipidemia, as evidenced by decreased total cholesterol and triglyceride levels, alongside increased high-density lipoprotein cholesterol levels. Histopathological analyses confirmed that HDPs-2A partially repaired liver tissue damage by mitigating oxidative stress responses in the liver. Additionally, treatment with HDPs-2A significantly elevated short-chain fatty acid levels in T2DM rats. Real-time quantitative PCR and Western blot analyses indicated that HDPs-2A significantly enhanced the expression of InsR, IRS2, PI3K, Akt, and GLUT4, suggesting that HDPs-2A regulates insulin resistance and glycometabolism through the activation of the PI3K/Akt signaling pathway. Furthermore, HDPs-2A appeared to modulate the expression of GS, GSK-3β, and FoxO1 to improve glucose metabolism and reduce insulin resistance. It also improved glucose metabolism by activating the AMPK pathway and modulating G6Pase and PEPCK expression. This study provides novel insights into the antidiabetic effects of HDPs, positioning them as promising nutritional agents for the management of T2DM.

In vitro antidiabetic evaluation of Bombax buonopozense methanol leaf extract

Diabetes mellitus (DM) is a major worldwide health burden that requires research into cost-effective treatment alternatives. It has been claimed that herbal medicines, have improved glucose metabolism in diabetics. It has been showed that several plant extracts are useful in preserving glucose homeostasis. Therefore, the present study aimed to evaluate the phytochemical and antidiabetic activities of Bombax buonopozense methanol leaf extracts. Standard methods were used for the identification of alkaloids, tannins, flavonoids, saponins, phenolics, cardiacglycosides and steroids. The enzyme inhibitory activities of the extracts of B. buonopozense was evaluated on α-amylase and α-glucosidase. The crude leaf extract of B. buonopozense exhibited a more effective inhibition on α-glucosidase with IC50 (Half maximal inhibitory concentration) values 888.20±35.06 μg/mL when compared to control (ascorbic acid) with values 1076±2.77 μg/mL. Fractions of ethyl acetate showed lower inhibitory property of alpha glucosidase with IC50 value 18.44±2.63 μg/mL compared to the control (ascorbic acid with IC50 value 16325±1318 μg/mL). This study showed the scientific basis for the traditional therapeutic usage of B. buonopozense by proven its antidiabetic activity in vitro. This is the first time that B. buonopozense’s antidiabetic efficacy and possible mechanisms have been documented.

Mulberry leaf extract ameliorates high-fat diet-induced obesity in mice by regulating the gut microbiota and metabolites

The increasing prevalence of obesity presents a notable challenge to global health. Mulberry leaves enriched with biologically active substances hold promise for alleviating obesity. This research assessed the efficacy of mulberry leaf extract (MLE) in mitigating obesity and metabolic disturbances in mice fed a high-fat diet (HFD). The results demonstrated that MLE, administered at both low (167 mg/kg) and high (333 mg/kg) doses, decreased weight gain and fat accumulation, improved glucose metabolism, enhanced insulin sensitivity, and reduced inflammation. Analysis of fecal samples via 16S rRNA sequencing revealed that MLE corrected the gut microbiota imbalance caused by HFD, lowering the Firmicutes/Bacteroidota ratio as well as increasing the relative abundances of Bifidobacterium, Faecalibaculum, Coriobacteriaceae_UCG-002, and Dubosiella. Additionally, serum non-targeted metabolomics analysis identified 19 key differential metabolites associated with MLE treatment, which were primarily related to glycerophospholipid metabolism and tryptophan metabolism. Correlation analysis revealed negative associations between Dubosiella and Coriobacteriaceae_UCG-002 with specific phospholipids, and positive associations of 5-hydroxyindoleacetate and quinoline-4,8-diol with Bifidobacterium and Coriobacteriaceae_UCG-002. These findings suggest that MLE is effective in treating obesity and underscores its potential as a functional food.

The gut microbiota-derived metabolite indole-3-propionic acid enhances leptin sensitivity by targeting STAT3 against diet-induced obesity.

Obesity is associated with the gut microbiome. Here, we report that gut commensal Clostridia bacteria regulate host energy balance through the tryptophan-derived metabolite indole-3-propionic acid (IPA). IPA acts as an endogenous leptin sensitiser to counteract obesity. Mechanistically, IPA is secreted from the gut into the circulation, and then targets to the STAT3 in the hypothalamic appetite regulation centre, promoting its phosphorylation and nuclear translocation, which enhances the body's response to leptin, and regulates the balance between appetite and energy metabolism. The in vitro pull-down assays involving site-directed mutagenesis demonstrate that Trp623 in the SH2 domain is the key binding site for STAT3-IPA interaction. High-fat diet (HFD), rather than genetic factors, induces excessive secretion of antimicrobial peptides by Paneth cells, inhibiting the growth of Clostridia in the gut and resulting in decreased production of the beneficial metabolite IPA. IPA or Clostridium sporogenes supplement effectively controls weight gain, improves glucose metabolism, and reduces inflammation in DIO mice. IPA fails to achieve such effects in ob/ob mice, while exogenous leptin administration restores the therapeutic effect of IPA. Our study suggests that the IPA-based gut-brain axis regulates host metabolism, and supplementation with microbiome-derived IPA could be a promising intervention strategy for treating obesity.

Assessing the Benefit of Dietary Choline Supplementation Throughout Adulthood in the Ts65Dn Mouse Model of Down Syndrome.

Down syndrome (DS) is the most common cause of early-onset Alzheimer's disease (AD). Dietary choline has been proposed as a modifiable factor to improve the cognitive and pathological outcomes of AD and DS, especially as many do not reach adequate daily intake levels of choline. While lower circulating choline levels correlate with worse pathological measures in AD patients, choline status and intake in DS is widely understudied. Perinatal choline supplementation (Ch+) in the Ts65Dn mouse model of DS protects offspring against AD-relevant pathology and improves cognition. Further, dietary Ch+ in adult AD models also ameliorates pathology and improves cognition. However, dietary Ch+ in adult Ts65Dn mice has not yet been explored; thus, this study aimed to supply Ch+ throughout adulthood to determine the effects on cognition and DS co-morbidities. We fed trisomic Ts65Dn mice and disomic littermate controls either a choline normal (ChN; 1.1 g/kg) or a Ch+ (5 g/kg) diet from 4.5 to 14 months of age. We found that Ch+ in adulthood failed to improve genotype-specific deficits in spatial learning. However, in both genotypes of female mice, Ch+ significantly improved cognitive flexibility in a reverse place preference task in the IntelliCage behavioral phenotyping system. Further, Ch+ significantly reduced weight gain and peripheral inflammation in female mice of both genotypes, and significantly improved glucose metabolism in male mice of both genotypes. Our findings suggest that adulthood choline supplementation benefits behavioral and biological factors important for general well-being in DS and related to AD risk.

Satiety Hormone LEAP2 After Low-Calorie Diet With/Without Endobarrier Insertion in Obesity and Type 2 Diabetes Mellitus.

The liver/foregut satiety hormone liver-expressed antimicrobial peptide 2 (LEAP2) is an inverse agonist at the acyl ghrelin receptor (GHSR), increasing after food intake and decreasing after bariatric surgery and short-term nonsurgical weight loss, but effects of long-term dietary weight loss are unknown. The objective of this study was to examine and compare the effects of these interventions on fasting and postprandial plasma LEAP2 and investigate potential metabolic mediators of changes in plasma LEAP2. Plasma LEAP2 was measured in a previously published 2-year trial comparing standard medical management (SMM) (including 600-kcal/day deficit) with duodenal-jejunal bypass liner (DJBL, Endobarrier) insertion (explanted after 1 year) in adults with obesity and inadequately controlled type 2 diabetes mellitus. In the SMM group (n = 25-37), weight decreased by 4.3%, 8.1%, 7.8%, and 6.4% at 2, 26, 50, and 104 weeks and fasting plasma LEAP2 decreased from baseline mean ± SD 15.3 ± 0.9 ng/mL by 1.7, 3.8, 2.1, and 2.0 ng/mL, respectively. Absolute/decreases in fasting plasma LEAP2 positively correlated with absolute/decreases in body mass index, glycated hemoglobin A1c, fasting plasma glucose, serum insulin, homeostatic model assessment for insulin resistance, and serum triglycerides. Despite greater weight loss in the DJBL group (n = 23-30) at 26 to 50 weeks (10.4%-11.4%), the decrease in fasting plasma LEAP2 was delayed and attenuated (vs SMM), which may contribute to greater weight loss by attenuating GHSR signaling. Plasma LEAP2 did not increase with weight regain from 50 to 104 weeks after DJBL explant, suggesting a new set point with weight loss maintenance. Increases in plasma LEAP2 after a 600-kcal meal (10.8%-16.1% at 1-2 hours) were unaffected by weight loss, improved glucose metabolism, or DJBL insertion (n = 9-25), suggesting liver rather than duodenum/jejunum may be the primary source of postprandial LEAP2 secretion. These findings add to our understanding of the regulation and potential physiological role of plasma LEAP2.

Gut Microbiota Modulates Fgf21 Expression and Metabolic Phenotypes Induced by Ketogenic Diet.

The ketogenic diet (KD) is a widely used intervention for obesity and diabetes, effectively reducing body weight and blood glucose levels. However, the molecular mechanisms by which the KD influences body weight and glucose metabolism are not fully understood. While previous research has shown that the KD affects the gut microbiota, the exact role of microbiota in mediating its metabolic effects remains unclear. In this study, we used antibiotics to eliminate the gut microbiota, confirming its necessity for the KD's impact on weight loss and glucose metabolism. We also demonstrated the significant role of FGF21 in these processes, through antibiotics intervention in Fgf21-deficient mice. Furthermore, we revealed that the KD alters serum valine levels via the gut microbiota, which in turn regulates hepatic Fgf21 expression and circulating FGF21 levels through the GCN2-eIF2α-ATF5 signaling pathway. Additionally, we demonstrated that valine supplementation inhibits the elevated expression of FGF21, leading to the reduced body weight and improved glucose metabolism of the KD-fed mice. Overall, we found that the gut microbiota from the KD regulates Fgf21 transcription via the GCN2-eIF2α-ATF5 signaling pathway. ultimately affecting body weight and glucose metabolism. Our findings highlight a complex regulatory network linking the KD, Fgf21 expression, and gut microbiota, offering a theoretical foundation for targeted therapies to enhance the metabolic benefits of the KD.

Heat-treated brown rice starch structure and effect on short-chain fatty acids and mouse intestinal microbiota

Rice with high resistant starch (RS) exhibits the potential to improve glucose metabolism, insulin sensitivity. In this study, using two rice varieties—Samgwang, a medium-amylose rice, and Dodamssal, a high-amylose rice containing RS—we analyzed the composition and molecular structural characteristics of brown rice and its starch and the effects on fasting blood glucose levels, fecal short-chain fatty acid (SCFA), and gut microbiota after 8 weeks of consumption in mice. The amylose content of heat-treated Samgwang (HS) and -Dodamssal (HD) was 21.0 ± 0.2 and 47.5 ± 0.3 %, respectively, while RS contents were 0.8 ± 0.0 and 14.7 ± 1.0 %. HD exhibited a C-type starch crystallinity with a lower proportion of short chains and a higher proportion of long chains compared to HS. HD-fed mice exhibited lower fasting blood glucose levels and the highest SCFA levels in their feces. They also had the highest abundance of Ruminococcus bromii, an RS-degrading bacterium, the highest positive correlation with Faecalicatena fissicatena (r = 0.9), and the highest negative correlation with Lachnoclostridium scindens and Lawsonibacter asaccharolyticus (r = −0.8). Overall, HD consumption can improve glucose metabolism by increasing intestinal SCFA production and can serve as a prebiotic dietary ingredient to improve obesity and diabetes.

Silymarin administration after cerebral ischemia improves survival of obese mice by increasing cortical BDNF and IGF1 levels.

Obesity is associated with a systemic inflammatory state that contributes to neuroinflammation and increases the risk of stroke at an early age. Stroke is the third leading cause of death worldwide and the leading cause of permanent disability. This work aimed to assess whether obesity-induced neuroinflammation can be a prognostic stroke factor that can be improved with oral administration of silymarin, an anti-inflammatory and neuroprotective drug. Male C57/Bl6 mice were used to establish an obesity model through a high-fat diet (HFD) for 12 weeks. Cerebral ischemia was performed with photothrombosis in the left motor cortex at the end of the diet. Following the induction of ischemia, silymarin (100 mg/kg) was administered orally for 14 days. Levels of pro-inflammatory (IL1β, TNFα, and MCP1) and anti-inflammatory markers (IL4, IL10), neurotrophic factors (IGF1, BDNF), and CX3CL1 were assessed in the cortex and striatum using ELISA. Mice on the HFD gained significantly more weight than control subjects and exhibited altered glucose metabolism, which was improved after silymarin treatment. The survival rate was significantly lower in HFD mice (52.2%) compared to control mice (86%). Silymarin treatment improved survival in both ischemic groups (non-diet control: 95.7%, HFD: 78.3%). Silymarin raised cortical TNFα, IL4, IL10, IGF1, BDNF, and CX3CL1 levels in the HFD group with stroke, while the striatum did not present relevant differences. Our findings suggest that silymarin improves glucose metabolism, possibly impacting post-stroke survival in obese mice. The increased levels of neurotrophic factors BDNF and IGF1, along with microglial regulatory factor CX3CL1, may contribute to the improved survival observed. These results indicate that silymarin could be a potential therapeutic option for managing neuroinflammation and enhancing post-stroke outcomes in obese individuals.