Body Insulin Resistance Research Articles

Effects of Bifidobacterium and rosuvastatin on metabolic-associated fatty liver disease via the gut–liver axis

Background/aimsResearch has indicated that treatment with rosuvastatin can improve liver pathology in metabolic-associated fatty liver disease (MAFLD) patients and that treatment with Bifidobacterium can improve MAFLD. Therefore, the effects of Bifidobacterium, rosuvastatin, and their combination on related indices in a rat model of diet-induced MAFLD need to be investigated.MethodsForty rats were divided into five groups: the normal diet group (N), high-fat diet (HFD) model group (M), HFD + probiotic group (P), HFD + statin group (S), and HFD + probiotic + statin group (P-S). To establish the MAFLD model, the rats in Groups M, P, S, and P-S were fed a HFD for 8 weeks. The treatments included saline in Group N and either Bifidobacterium, rosuvastatin, or their combination in Groups P, S, and P-S by intragastrical gavage. After 4 weeks of intervention, the rats were euthanized, and samples were harvested to analyze gastrointestinal motility and liver function, pathological changes, inflammatory cytokine production, and the expression of proteins in key signaling pathways.ResultsHFD feeding significantly increased the body weight, liver index, and insulin resistance (IR) index of the rats, indicating that the MAFLD model was successfully induced. Bifidobacterium reduced the liver of MAFLD rats, while Bifidobacterium with Rosuvastatin decreased the liver index, IR index, and levels of aspartate aminotransferase and alanine aminotransferase in MAFLD rats. The MAFLD model showed altered expression of proteins in signaling pathways that regulate inflammation, increased production of inflammatory cytokines, an elevated MAFLD activity score (MAS), and pathological changes in the liver. The MAFLD model also showed reduced relative counts of intestinal neurons and enteric glial cells (EGCs), altered secretion of gastrointestinal hormones, and slowed gastrointestinal emptying. Bifidobacterium, rosuvastatin, or their combination inhibited these various changes. HFD feeding changed the rats’ gut microbiota, and the tested treatments inhibited these changes. These results suggest that the gastrointestinal motility disorder and abnormal liver function in MAFLD rats may be related to a reduction in Escherichia-Shigella bacteria and an increase in Asticcacaulis bacteria in the gut microbiota and that the improvement in liver function induced by Bifidobacterium plus rosuvastatin may be related to increases in Sphingomonas and Odoribacter bacteria and a decrease in Turicibacter bacteria in the gut microbiota.ConclusionsThe combined use of Bifidobacterium and rosuvastatin could better regulate the gut microbiota of MAFLD model rats, promote gastrointestinal emptying, and improve liver pathology and function than single treatment with Bifidobacterium or rosuvastatin. This provides a better strategy for the treatment of MAFLD.

Relationship Between Body Composition and Insulin Resistance Evaluated by the TyG Index: A Retrospective Study Among Chinese Population

ABSTRACTObjectiveThe triglyceride glucose (TyG) index, a novel and easily obtained marker of insulin resistance (IR), has been shown to predict metabolic diseases. Monitoring body composition is crucial in assessing disease states. This study aimed to investigate the relationship between body composition and IR as assessed by the TyG index.MethodsBetween January 2018 and December 2021, 12,186 individuals were initially enroled, with 4061 adults were ultimately included. Body composition, including fat mass (FM), fat mass index (FMI), fat‐free mass (FFM), fat‐free mass index (FFMI), and percent body fat (PBF), was measured using bioelectrical impedance analysis. Spearman analysis assessed correlations between body composition indices and the TyG index. Binary logistic regression identified independent predictors of IR.ResultsOlder women (≥ 50 years old) showed significantly higher BMI, PBF, FM, FMI, FFMI, HOMA‐IR, and the TyG index, but lower FFM compared to younger women; Older men exhibited significantly lower BMI, FM, FFM, FFMI, HOMA‐IR, and the TyG index than the younger men. FM, FMI, FFM, FFMI, and PBF were positively correlated with the TyG index. FFMI and PBF significantly predicted IR in both genders. Combined FFMI and PBF yielded an area under the ROC curves of 0.718 in women and 0.661 in men for IR diagnosis.ConclusionThe TyG index correlates with body composition parameters of FFMI and PBF as well as HOMA‐IR potentially making it a convenient marker of metabolic risk.

Anti-Diabetic Effects of <i>Cordyceps Militaris</i> Extract on Weight, Blood Glucose, and Insulin Resistance in Diabetic Model Mice

Objectives: This study investigates the anti-diabetic effects of <i>Cordyceps militaris</i> extract on diabetic model mice (db/db mouse).Methods: Diabetic mice (db/db) were compared to normal control group (NC). The positive control group received Metformin (Met), while other groups received <i>Cordyceps militaris</i> extract, including <i>ARA301_L</i>. Body weight, fasting blood glucose levels (FBGL), oral glucose tolerance tests (OGTT), insulin tolerance tests (ITT), blood lipid profiles, and tissue analysis were conducted.Results: Diabetic mice showed significantly higher body weight compared to normal mice. The positive control group maintained stable weight over 56 days, while the <i>Cordyceps militaris</i> extract groups showed slight weight decreases, with a marked reduction in the <i>ARA301_L</i> group. FBGLs were significantly lower in treated groups than in control groups. OGTT indicated better glucose regulation in treated groups, though differences among them were not significant. ITT showed lower blood glucose levels in treated groups, indicating improved insulin resistance. Blood lipid profiles revealed significant reductions in total cholesterol (TC) and AST in the <i>ARA301_L</i> group. Liver tissue analysis showed decreased expression of lipid metabolism and inflammation-related genes, particularly PPAR<i>γ</i> and SREBP-1c. Muscle and adipose tissues displayed increased GLUT4 protein and reduced inflammatory gene expression.Conclusions: <i>Cordyceps militaris</i> extract has more positive effects than metformin on body weight, insulin resistance, sugar metabolism, fatty liver, and inflammation in diabetic mice. It also has a similar positive effect as metformin on blood lipid concentration and liver damage. This suggests the potential of diabetes management in <i>Cordyceps militaris</i> extract.

GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells

The use of incretin agonists for managing metabolic dysfunction-associated steatohepatitis (MASH) is currently experiencing considerable interest. However, whether these compounds have a direct action on MASH is still under debate. This study aims to investigate whether GLP-1R/GIPR agonists act directly in hepatocytes and hepatic stellate cells (HSCs). For this, human hepatocyte and HSCs lines, as well as primary human hepatocytes and HSCs treated with Liraglutide, Acyl-GIP or the GLP-1/GIP dual agonist (MAR709) were used. We show that the concentrations of each compound, which were effective in insulin release, did not induce discernible alterations in either hepatocytes or HSCs. In hepatocytes displaying elevated fatty acid content after the treatment with oleic acid and palmitic acid, none of the three compounds reduced lipid concentration. Similarly, in HSCs activated with transforming growth factor-β (TGFb), Liraglutide, Acyl-GIP and MAR709 failed to ameliorate the elevated expression of fibrotic markers. The three compounds were also ineffective in phosphorylating CREB, which mediates insulinotropic actions, in both hepatocytes and HSCs. These findings indicate that incretin agonists have no direct actions in human hepatocytes or hepatic stellate cells, suggesting that their beneficial effects in patients with MASH are likely mediated indirectly, potentially through improvements in body weight, insulin resistance and glycemic control.

Clopidogrel ameliorates high-fat diet-induced hepatic steatosis in mice through activation of the AMPK signaling pathway and beyond.

Metabolic dysfunction-associated steatotic liver disease (MASLD) frequently confers an increased risk of vascular thrombosis; however, the marketed antiplatelet drugs are investigated for the prevention and treatment of MASLD in patients with these coexisting diseases. To determine whether clopidogrel could ameliorate high-fat diet (HFD)-induced hepatic steatosis in mice and how it works, mice were fed on normal diet or HFD alone or in combination with or without clopidogrel for 14weeks, and primary mouse hepatocytes were treated with palmitate/oleate alone or in combination with the compounds examined for 24h. Body weight, liver weight, insulin resistance, triglyceride and total cholesterol content in serum and liver, histological morphology, transcriptomic analysis of mouse liver, and multiple key MASLD-associated genes and proteins were measured, respectively. Clopidogrel mitigated HFD-induced hepatic steatosis (as measured with oil red O staining and triglyceride kit assay) and reduced elevations in serum aminotransferases, liver weight, and the ratio of liver to body weight. Clopidogrel downregulated the expression of multiple critical lipogenic (Acaca/Acacb, Fasn, Scd1, Elovl6, Mogat1, Pparg, Cd36, and Fabp4), profibrotic (Col1a1, Col1a2, Col3a1, Col4a1, Acta2, and Mmp2), and proinflammatory (Ccl2, Cxcl2, Cxcl10, Il1a, Tlr4, and Nlrp3) genes, and enhanced phosphorylation of AMPK and ACC. However, compound C (an AMPK inhibitor) reversed enhanced phosphorylation of AMPK and ACC in clopidogrel-treated primary mouse hepatocytes and alleviated accumulation of intracellular lipids. We concluded that clopidogrel may prevent and/or reverse HFD-induced hepatic steatosis in mice, suggesting that clopidogrel could be repurposed to fight fatty liver in patients.

Nonlinear association between alanine aminotransferase to high-density lipoprotein cholesterol ratio and risk of gestational diabetes mellitus

Previous studies have indicated a potential association between the alanine aminotransferase to high-density lipoprotein cholesterol (ALT/HDL-C) ratio and the risk of Type 2 Diabetes Mellitus, but its relation with gestational diabetes mellitus (GDM) remains uncertain. This study aims to investigate the correlation between the ALT/HDL-C ratio in early pregnancy and the risk of GDM. This study is a secondary analysis based on an open-source cohort study. A total of 590 single pregnant women attending two hospitals in Korea up to 14 weeks gestation were included between November 2014 and July 2016. Logistic regression analysis, subgroup analysis, and smooth curve fitting were employed to explore the association between the ALT/HDL-C ratio and GDM risk. The predictive capability of the ALT/HDL-C ratio for GDM was assessed using ROC curve analysis. The average age of participants was 32.06 ± 3.80 years, with a GDM incidence rate of 6.27%. Multifactorial logistic regression analysis revealed that the serum ALT/HDL-C ratio is an independent influencing factor for GDM (OR = 1.08, 95% CI: 1.02–1.16). Furthermore, a non-linear relationship between the ALT/HDL-C ratio and GDM risk was observed, with a turning point at 5.51. The effect size (OR) on the left and right sides of the turning point were 0.75 (95% CI: 0.37–1.59) and 1.55 (95% CI: 1.18-2.00), respectively. Additionally, when combined with age, pre-pregnancy body mass index, parity, and insulin resistance index in a prediction model for GDM, the ALT/HDL-C ratio demonstrated improved sensitivity of prediction by reaching up to 67.6%, specificity of prediction by reaching up to 87.3%, and an area under curve value of 0.819 (95%CI: 0.743–0.894). In early pregnancy, the serum ALT/HDL-C ratio shows a positive correlation with maternal risk in a nonlinear manner. The combination of ALT/HDL-C ratio with maternal characteristics and metabolic indicators provides good predictive value for GDM. This study may facilitate optimization of GDM prevention in pregnant women and enable timely and effective intervention to enhance their prognosis.

Delphinidin or α-amyrin attenuated liver steatosis and metabolic disarrangement in rats fed a high-fat diet.

Non-alcoholic fatty liver disease (NAFLD) is a liver pathology concomitant with metabolic disarrangement. This study assessed the therapeutic impacts of delphinidin, an anthocyanin, or α-amyrin, a pentacyclic triterpenoid, on NAFLD in rats and the underlying mechanisms involved. NAFLD was established by feeding a high-fat diet (HFD) for 10 weeks, either alone or in combination with delphinidin (40 mg/kg, oral) or α-amyrin (20 mg/kg, oral). Delphinidin or α-amyrin ameliorated the metabolic and histopathological perturbations induced by HFD. These compounds markedly attenuated NAFLD-induced hepatic steatosis, as evidenced by a substantial decrease in body weight, insulin resistance, and liver and adipose tissue indices. Alongside normalization of the atherogenic index, both improved HFD-mediated abnormalities in serum lipids, liver enzymes, leptin, and ghrelin levels. Moreover, their intervention activated the NFE2 like bZIP transcription factor 2 and heme oxygenase 1 pathways and abrogated HFD-triggered activation of mitogen-activated protein kinase 1 signaling. These remedies inhibited hepatic apoptosis and modulated the gene expression of lipogenic enzymes. Furthermore, histological analysis corroborated the suppression of lipid accumulation and amelioration of hepatic architecture in the treated rats. Our findings highlight the hepatoprotective value of delphinidin or α-amyrin against NAFLD and related metabolic diseases through their insulin-sensitizing, anti-inflammatory, antioxidant, and antiapoptotic effects.

Light modulates glucose and lipid homeostasis via the sympathetic nervous system.

Light is an important environmental factor for vision, and for diverse physiological and psychological functions. Light can also modulate glucose metabolism. Here, we show that in mice, light is critical for glucose and lipid homeostasis by regulating the sympathetic nervous system, independent of circadian disruption. Light deprivation from birth elicits insulin hypersecretion, glucagon hyposecretion, lower gluconeogenesis, and reduced lipolysis by 6-8 weeks, in male, but not, female mice. These metabolic defects are consistent with blunted sympathetic activity, and indeed, sympathetic responses to a cold stimulus are significantly attenuated in dark-reared mice. Further, long-term dark rearing leads to body weight gain, insulin resistance, and glucose intolerance. Notably, metabolic dysfunction can be partially alleviated by 5 weeks exposure to a regular light-dark cycle. These studies provide insight into circadian-independent mechanisms by which light directly influences whole-body physiology and inform new approaches for understanding metabolic disorders linked to aberrant environmental light conditions.

Effects of Ginseng Consumption on Cardiovascular HealthBiomarkers in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Ginseng, with various pharmacological activities, has received increasing attention to improve cardiovascular health (CVH). Therefore, this meta-analysis synthesized the effect of ginseng consumption on biomarkers of CVH in adults. A systematic search was performed in the databases of PubMed, Scopus, Web of Science, Embase, and the Cochrane Library through July 24, 2023 to screen out English-language randomized controlled trials (RCTs) evaluating the effects of ginseng consumption on body composition, blood pressure, vascular stiffness, lipid metabolism, glucose metabolism, insulin resistance, inflammatory cytokines, and adipocytokines in adults. The weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate the overall effect size, and STATA 12.0 was used for comprehensive analysis. Forty-five studies were included in the meta-analysis. Ginseng consumption significantly reduced systolic blood pressure (SBP) (WMD = -2.57 mmHg, 95% CI = -4.99 to -0.14, p = 0.038), total cholesterol (TC) (WMD = -4.40 mg/dL, 95% CI = -8.67 to -0.132, p = 0.043), low density lipoprotein cholesterol (LDL-C) (WMD = -2.81 mg/dL, 95% CI = -4.89 to -0.72, p = 0.008), C-reactive protein (CRP) (WMD = -0.41 mg/L, 95% CI = -0.73 to -0.10, p = 0.010), and interleukin-6 (IL-6) (WMD = -2.82 pg./mL, 95% CI = -4.31 to -1.32, p < 0.001). Subgroup analyses suggested that supplementation with ginseng for less than 12 weeks significantly reduced SBP, but 12 weeks or more improved TC and CRP. Ginseng consumption on SBP, TC, and CRP seemed to be more effective on unhealthy participants. The meta-analysis showed that ginseng consumption might have the potential to improve SBP, TC, LDL-C, CRP, and IL-6. These findings suggest that ginseng is a potential candidate for the maintenance of CVH. However, our results had high heterogeneity. Future high-quality studies are needed to firmly establish the clinical efficacy of ginseng consumption.

5124 Increased Copeptin May Reflect Vasopressin-Related Metabolic Changes After Bariatric Surgery

Abstract Disclosure: F. Galbiati: None. A. Aulinas Maso: None. I. Becetti: None. M. Lauze: None. V. Singhal: None. E.A. Lawson: Research Investigator; Self; received research funding and study drug from Tonix Pharmaceuticals. M. Bredella: None. M. Bredella: None. M. Misra: Advisory Board Member; Self; key opinion leader for Lumos Pharma. Consulting Fee; Self; Up To Date, Receives royalties. Objective: Vasopressin (AVP) is a neurohormone that decreases fat mass, promotes muscle regeneration, improves glucose homeostasis, and protects against hypoglycemia in animals and humans. Copeptin, a stable cleavage product of AVP, is positively associated with body mass index (BMI), insulin resistance, and metabolic syndrome in adults, suggesting an adaptive increase in AVP to counteract metabolic disruption. Similarly, copeptin was positively correlated with BMI in children. Metabolic and bariatric surgery (MBS) is highly effective at reducing metabolic complications of obesity, and underlying mechanisms may provide insights into novel therapeutics for obesity management. No study has investigated copeptin pre- and post-MBS in humans. We hypothesized that after MBS, (1) copeptin would increase and (2) increased copeptin would be associated with improved metabolic parameters. Methods: Longitudinal study in 64 adolescents and young adults (78% females; age [mean±SD] 18.7±2.8 years) with obesity (BMI 45.6±6.8 kg/m2). 34 underwent MBS (sleeve gastrectomy or Roux-en-Y gastric bypass) and 30 underwent non-surgical (NS) lifestyle management. We measured fasting circulating copeptin, %fat, and lean mass by dual-energy X-ray absorptiometry, hemoglobin A1c (HbA1c), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at baseline and 12 months. Results: Groups were similar for age, sex, race, and pubertal stage. Baseline BMI and %fat were higher in MBS (p≤.012). Baseline copeptin, %lean mass, HbA1c, and HOMA-IR did not differ across groups (p≥.103). MBS vs NS 12-month changes were [median(IQR)]: BMI -29.0 (-33.7, -16.5)% and 0.54 (-3.10, +4.37)%; %fat -8.03 (-13.33, -4.25) and -0.68 (-2.92, 0.64); %lean mass 7.73 (3.45, 12.38) and 0.83 (-.58, 2.73); HbA1c -0.40 (-0.52, -0.20) and -0.10 (-0.20, -0.02); HOMA-IR (mean±SD) -2.47±2.17 and 0.76±2.42 (ps≤.001). Baseline copeptin was correlated negatively with %fat (rho=-.25; p=.045), and positively with %lean mass (trend-level rho=.25, p=0.051). Copeptin increased in the MBS group and decreased in the NS group (time-x;-treatment effect: p=.017). Overall, copeptin change was correlated negatively with %fat change (rho=-.29; p=.025) and positively with %lean mass change (trend-level rho=0.24, p=.070). Copeptin change was positively correlated with changes in %lean mass (rho=.37, p=.045), HbA1c (rho=.46; p=.010), and HOMA-IR (rho=.53; p=.004), only after MBS. Conclusion: Overall, increase in copeptin over 12 months was associated with improved body composition, suggesting that increased AVP following MBS may contribute to its associated metabolic improvements. However, within the MBS group, improved glucose homeostasis was associated with reductions in copeptin, suggesting a possible protective mechanism against post-bariatric hypoglycemia. Presentation: 6/2/2024

Impact of Gut Microbiota and SCFAs in the Pathogenesis of PCOS and the Effect of Metformin Therapy.

Polycystic ovary syndrome (PCOS) is a complex disorder that impacts both the endocrine and metabolic systems, often resulting in infertility, obesity, insulin resistance, and cardiovascular complications. The aim of this study is to investigate the role of intestinal flora and its metabolites, particularly short-chain fatty acids (SCFAs), in the development of PCOS, and to assess the effects of metformin therapy on these components. SCFA levels in fecal and blood samples from women with PCOS (n=69) and healthy controls (n=18) were analyzed using Gas Chromatography-Mass Spectrometry (GC/MS) for precise measurement. Fecal microbiota were quantitatively detected by real-time polymerase chain reaction (PCR). To assess the efficacy of six months of metformin treatment, changes in the microbiota and SCFAs in the PCOS group (n=69) were also evaluated. The results revealed that women with PCOS exhibited a significant reduction in beneficial bacteria (namely, the C. leptum group and Prevotella spp.) alongside a notable overgrowth of opportunistic microorganisms (C. perfringens, C. difficile, Staphylococcus spp., and Streptococcus spp.). An overproduction of acetic acid (AA, FC=0.47, p<0.05) and valeric acid (VA, FC=0.54, p<0.05) suggests a link between elevated SCFAs and the development of obesity and PCOS. Interestingly, AA in the bloodstream might offer a protective effect against PCOS by ameliorating key symptoms such as high body mass index (r=-0.33, p=0.02), insulin resistance (r=-0.39, p=0.02), and chronic inflammation. Although serum SCFA levels showed non-significant changes following metformin treatment (p>0.05), the normalization of AA in the gut underscores that metformin exerts a more pronounced effect locally within the gastrointestinal tract. Furthermore, the study identified the most effective model for predicting the success of metformin therapy, based on serum concentrations of butyric acid (BA) and VA, achieving a 91% accuracy rate, 100% sensitivity, and 80% specificity. These promising findings highlight the potential for developing targeted interventions and personalized treatments, ultimately improving clinical outcomes for women with PCOS.

Orexins mitigate obesity-associated dysfunctions in mice.

Obesity is a chronic disease that affects more than 400 million adults with severe comorbidities. The search for new treatments to reduce its negative consequences is necessary. Orexins are hypothalamic neuropeptides involved in various physiological processes related to obesity. The aim of this study was to investigate the consequences of chronic orexin-A treatment in mouse models. Female wild-type C57BL/6 mice that were obesity-prone or obesity-resistant and mice that were deficient for orexin receptors were fed with a high-fat diet. Glucose tolerance, indirect calorimetry, expression of brain neuropeptides and receptors, microglial activation, and microbiota were determined to evaluate the role of orexins on metabolic flexibility. Orexin-A reduces weight gain in obesity-prone mice. This reduction is associated with a decrease in body fat, food intake, steatosis, and insulin resistance, as well as alterations of intestinal microbiota composition. A decreased expression of orexin receptors and neuropeptides involved in food intake was also observed in the hypothalamus. Our data support the notion that orexin receptor signaling is involved in different aspects of energy metabolism and can mitigate several dysfunctions associated with obesity, suggesting that orexin receptors can represent new targets for obesity treatment.

Subclinical left ventricular structural and functional alterations in children with obesity: is body mass or insulin resistance the main issue?

Obesity is an independent risk factor for cardiovascular diseases. The study aims to assess the left ventricular structure and functions in children with obesity. This study included 29 patients with metabolic syndrome, 31 patients with obesity without metabolic syndrome, and 30 healthy children of similar age and gender. Demographic, anthropometric, and biochemical findings and left ventricular structure and functions evaluated by conventional pulsed wave Doppler and tissue Doppler echocardiography were compared. The left ventricular mass index and relative wall thickness were significantly higher in children with obesity compared to controls. The mean left ventricular mass index of children with metabolic syndrome was also higher than for those without it. Most children with obesity had normal left ventricular geometry; concentric hypertrophy (27.6%) was more common in children with metabolic syndrome, and eccentric hypertrophy (25.7%) was more common in those without. The early to late diastolic mitral annular velocity ratios obtained with conventional pulsed wave Doppler echocardiography and tissue Doppler echocardiography (E/A and Em/Am, respectively) were lower in children with obesity than controls. In addition, the ratio obtained by tissue Doppler echocardiography was lower in children with metabolic syndrome than without. The homeostatic model assessment of insulin resistance, systolic blood pressure, and body mass index has been identified as independent factors for left ventricular structures and functions. Obesity causes subclinical left ventricular hypertrophy and diastolic dysfunction. Additional metabolic syndrome-related risks lead to further deterioration of cardiac morphology and functions.

A Randomized Trial of the Efficacy of Three Weight Loss Diet Interventions in Overweight/Obese with Polycystic Ovary Syndrome.

Polycystic Ovary Syndrome (PCOS) is a highly prevalent, complex, heterogeneous, polygenic endocrine disorder characterized by metabolic and reproductive dysfunction that affects 8-13% of women of reproductive age worldwide. The pathogenesis of PCOS has not been fully clarified and includes genetics, obesity, and insulin resistance (IR). Oxidative stress (OS) of PCOS is independent of obesity. It can induce IR through post-insulin receptor defects, impair glucose uptake in muscle and adipose tissue, and exacerbate IR by reducing insulin secretion from pancreatic β-cells. To investigate the effects of Calorie Restricted Diet (CRD), High Protein Diet (HPD), and High Protein and High Dietary Fiber Diet (HPD+HDF) on body composition, insulin resistance, and oxidative stress in overweight/obese PCOS patients. A total of 90 overweight/obese patients with PCOS were selected to receive an 8- week medical nutrition weight loss intervention at our First Hospital of Peking University, and we randomly divided them into the CRD group (group A), the HPD group (group B), and the HPD+HDF group (group C), with 30 patients in each group. We measured their body composition, HOMA-IR index, and oxidative stress indicators. The t-test, Mann-Whitney U test, analysis of variance (ANOVA), and Kruskal-Wallis H test were used to compare the efficacy of the three methods. After eight weeks, the body weights of the three groups decreased by 6.32%, 5.70% and 7.24%, respectively, and the Visceral Fat Area (VFA) values decreased by 6.8 cm2, 13.4 cm2 and 23.45 cm2, respectively, especially in group C (p <0.05). The lean body mass (LBM), also known as the Fat-Free Mass (FFM) values of group B and group C after weight loss, were higher than that of group A (p <0.05). After weight loss, the homeostatic model assessment of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) were decreased. Superoxide dismutase (SOD) was increased in all three groups (p <0.05), and the changes in SOD and MDA in group B and group C were more significant (p <0.05). HOMA-IR index positively correlated with body mass index (BMI) (r=0.195; p <0.05); MDA positively correlated with percent of body fat (PBF) (r=0.186; p <0.05) and HOMA-IR index (r=0.422; p <0.01); SOD positively correlated with LMI/FFMI (r=0.195; p <0.05), negatively correlated with HOMA-IR index (r=-0.433; p <0.01). All three diets were effective in reducing the body weight of overweight/obese patients with PCOS by more than 5% within 8 weeks and could improve both insulin resistance and oxidative stress damage. Compared with CRD, HPD and HPD+HDF diets could better retain lean body mass and significantly improve oxidative stress damage.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce the risk of developing cancer-related lymphedema following axillary lymph node dissection (ALND).

Patients undergoing axillary lymph node dissection (ALND) for breast cancer face a high risk of lymphedema, further increased by high body mass index (BMI) and insulin resistance. GLP-1 receptor agonists (GLP-1RAs) have the potential to reduce these risk factors, but their role in lymphedema has never been investigated. The purpose of this study was to determine if GLP-RAs can reduce the risk of lymphedema in patients undergoing ALND. All patients who underwent ALND at a tertiary cancer center between 2010 and 2023 were reviewed. Patients with less than 2years of follow-up from the time of ALND were excluded. Race, BMI, radiation, chemotherapy history, pre-existing diagnosis of diabetes, lymphedema development after ALND, and the use of GLP-1RAs were analyzed. Multivariate logistic regression analysis was performed to assess if there was a significant reduction in the risk of developing lymphedema after ALND. A sub-group analysis of non-diabetic patients was also performed. 3,830 patients who underwent ALND were included, 76 of which were treated with. GLP-1 RAs. The incidence of lymphedema in the GLP-1 RA cohort was 6.6% (5 patients). Compared to 28.5% (1,071 patients) in the non-GLP-1 RA cohort. On multivariate regression analysis, patients who were treated with GLP-1 RA were 86% less likely to develop lymphedema compared to the non-GLP-1 RA cohort (OR 0.14, 95% CI 0.04-0.32, p < 0.0001). A BMI of 25kg/m 2 or greater was a statistically significant risk factor for developing lymphedema with an odds ratio of 1.34 (95% CI 1.16-1.56, p < 0.0001). Diabetes was associated with lymphedema development that closely approached statistical significance (OR 1.32, 95% CI 0.97-1.78, p = 0.06). A subgroup analysis solely on non-diabetic patients showed similar results. The odds of developing lymphedema were 84% lower for patients without diabetes treated with GLP1-RAs compared to those who did not receive GLP-1 RAs (OR 0.16, 95% CI 0.05-0.40, p < 0.0001). GLP1-RAs appear to significantly reduce the risk of lymphedema in patientsundergoing ALND. The mechanism of action may be multifactorial and not limited to weight reduction and insulin resistance. Future prospective analysis is warranted to clarify the role of GLP-1RAs in reducing lymphedema risk.

Comparison of Adiposomal Lipids between Obese and Non-Obese Individuals.

Our recent findings revealed that human adipose tissues (AT)-derived extracellular vesicles (adiposomes) vary in cargo among obese and lean individuals. The main objective of this study was to investigate the adiposomal lipid profiles and their correlation with cardiometabolic risk factors. AT samples were collected from obese subjects and lean controls and analyzed for their characteristics and lipid content. In addition, we measured the correlation between adiposomal lipid profiles and body composition, glucose and lipid metabolic profiles, brachial artery vasoreactivity, AT arteriolar flow-induced dilation, and circulating markers such as IL-6, C-reactive protein, and nitric oxide (NO). Compared to lean controls, adiposomes isolated from obese subjects were higher in number after normalization to AT volume. The two major lipid classes differentially expressed were lysophosphatidylcholine/phosphatidylcholine (LPC/PC) and ceramides (Cer). All lipids in the LPC/PC class were several-fold lower in adiposomes from obese subjects compared to lean controls, on top of which were PC 18:2, PC 18:1, and PC 36:3. Most ceramides were markedly upregulated in the obese group, especially Cer d37:0, Cer d18:0, and Cer d39:0. Regression analyses revealed associations between adiposomal lipid profiles and several cardiometabolic risk factors such as body mass index (BMI), fat percentage, insulin resistance, arteriolar and brachial artery vasoreactivity, NO bioavailability, and high-density lipoproteins (HDL-C). We conclude that the ability of adiposomes from obese subjects to disrupt cardiometabolic function could be partly attributed to the dysregulated lipid cargo.

Agave-Laurate-Bioconjugated Fructans Decrease Hyperinsulinemia and Insulin Resistance, Whilst Increasing IL-10 in Rats with Metabolic Syndrome Induced by a High-Fat Diet.

Metabolic syndrome (MetS) comprises a cluster of metabolic risk factors, which include obesity, hypertriglyceridemia, high blood pressure, and insulin resistance. The purpose of this study was to evaluate the effects of laurate-bioconjugated fructans on pro- and anti-inflammatory cytokines in Wistar rats with MetS induced by a high-fat diet. Laurate-bioconjugated fructans were synthesized with agave fructans, immobilized lipase B, and vinyl laureate as the acylant. Groups were fed a standard diet (NORMAL), a high-fat diet (HFD), or a high-fat diet plus laurate-bioconjugated fructans (FL PREV) for 9 weeks. A fourth group received a high-fat diet for 6 weeks, followed by simultaneous exposure to a high-fat diet and laurate-bioconjugated fructans for 3 additional weeks (FL REV). The dose of laurate-bioconjugated fructans was 130 mg/kg. Laurate-bioconjugated fructans reduced food and energy intake, body weight, body mass index, abdominal circumference, adipose tissue, adipocyte area, serum triglycerides, insulin, insulin resistance, and C-reactive protein but they increased IL-10 protein serum levels and mRNA expression. The impact of laurate-bioconjugated fructans on zoometric and metabolic parameters supports their potential as therapeutic agents to improve obesity, obesity comorbidities, insulin resistance, type 2 diabetes mellitus, and MetS.

The Association between Body Composition Phenotype and Insulin Resistance in Post-COVID-19 Syndrome Patients without Diabetes: A Cross-Sectional, Single-Center Study.

The most frequent body composition alterations in post-COVID-19 syndrome include low muscle mass, dynapenia, sarcopenia, and obesity. These conditions share interconnected pathophysiological mechanisms that exacerbate each other. The relationship between body composition phenotypes and metabolic abnormalities in post-COVID-19 syndrome remains unclear. To evaluate the association between body composition phenotypes and insulin resistance (IR) and metabolic abnormalities in non-diabetic individuals with post-COVID-19 syndrome. A cross-sectional, single-center study involving 483 subjects with post-COVID-19 syndrome following moderate to severe acute COVID-19 requiring hospitalization. Individuals with diabetes, those who declined to participate, or those who could not be contacted were excluded. Body composition phenotypes were classified as normal weight, dynapenia, sarcopenia, dynapenic obesity, and sarcopenic obesity (SO). The average age was 52.69 ± 14.75 years; of note, 67.08% were male. The prevalence of body composition phenotypes was as follows: 13.25% were of normal weight, 9.52% had dynapenia, 9.94% had sarcopenia, 43.69% had obesity, 18.84% had dynapenic obesity, and 4.76% had SO. Additionally, 58.18% had IR. Obesity (OR: 2.98, CI95%; 1.64-5.41) and dynapenic obesity (OR: 4.98, CI95%; 1.46-6.88) were associated with IR. The most common body composition phenotypes were obesity, dynapenic obesity, and dynapenia. Furthermore, obesity and dynapenic obesity were associated with IR in post-COVID-19 syndrome.

The correlation of BMI and insulin resistance in moderately burned patients.

&lt;b&gt;Introduction:&lt;/b&gt; Obesity is strongly related to serious comorbidities that might affect the healing process. Elevated Body Mass Index (BMI) and insulin resistance have a significant impact on the development of the metabolic syndrome often leading to lethal cardiovascular complications.&lt;b&gt;Aim:&lt;/b&gt; The aim of the study was to verify the correlation of BMI and insulin resistance with clinical parameters of moderately burned patients.&lt;b&gt;Materials and methods:&lt;/b&gt; There were 149 patients enrolled in the study and their clinical data was retrospectively analyzed. The laboratory tests, insulin demand, BMI, and surgical procedures were evaluated on admission and discharge.&lt;b&gt;Results:&lt;/b&gt; Burned patients who required insulin were characterized by worse laboratory results on admission to the burn unit, they had lower hemoglobin (HGB) levels (P = 0.0001), higher creatinine levels by 0.323 units (P = 0.009), higher C-reactive protein (CRP) by approximately 94 units (P = 0.0001), as higher procalcitonin (PCT) by approximately 0.5 units (P = 0.001) as compared to non-insulin-treated patients. Moreover, burned patients who required insulin stayed in the hospital for an average of 10 days longer. All patients from the insulin-demand subgroup had elevated triglycerides (Tg) levels on admission with increased indexes of insulin resistance.&lt;b&gt;Discussion:&lt;/b&gt; Our study suggests that the protective effect of a higher BMI in burned patients, known as the 'obesity paradox' may be compromised by insulin resistance.&lt;b&gt;Conclusions and significance of the study:&lt;/b&gt; The results show that elevated Tg on admission to the burn unit coexisting with a BMI over 25 kg/m&lt;sup&gt;2&lt;/sup&gt; may be used as an important prognostic factor and may help with prediction of insulin demand and worse outcome in moderately burned patients.

Insulin-Resistant Male LEW.1WR1 Rats Do Not Develop β-Cell Mass Expansion in Response to a Moderate Sucrose Diet

Characterizing changes in beta cell function during prolonged hyperinsulinemia and dietary stress is important to study to prevent diseases like metabolic dysfunction-associated steatotic liver disease and insulin resistance. This research investigates how a moderate sucrose (MS) diet affects insulin resistance and β-cell mass in two rat strains: LEW.1WR1 and Wistar Furth (WF). LEW.1WR1 rats seem to be sensitive to beta cell disruptions as weanlings. Twenty-one male LEW.1WR1 rats and sixteen male WF rats were studied over 18 weeks. The rats were divided into groups and given either the control or MS diet. Their body weight was monitored twice a week. Insulin tolerance tests (ITTs) and fasting blood glucose measurements were taken at intervals. Urine samples were analyzed to assess metabolic shifts, and pancreas tissue was examined to evaluate changes in β-cell mass. The LEW.1WR1 rats became overweight and showed higher insulin resistance than the WF rats. Both strains of rats on the MS diet displayed changes in urine metabolite profiles in terms of levels of lactic acid and alanine. This study highlights the impact or lack thereof of a moderate sucrose diet on body mass, insulin resistance, and β-cell mass, with notable effects observed specifically in LEW.1WR1 rats. These findings contribute to our understanding of how dietary sugar intake can affect metabolism when observed in models sensitive to metabolic defects.