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Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary and exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid and glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging and histological grading) for all patients of the original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting glucose (FG), hs-CRP, ferritin, diastolic BP and steatosis improved significantly, independent of diabetes status: most patients with prediabetes returned to normal FG levels. Significant adiponectin increases correlated with hepatic and CMH marker improvement; patients had an average weight gain of 2.5 kg, with 49% gaining ≥2.5% weight. Therapeutic benefits were similar regardless of weight change. Here, we show that effects of lanifibranor on liver histology in MASH are accompanied with CMH improvement, indicative of potential cardiovascular clinical benefits. Cardiovascular events are the main cause of mortality in patients with metabolic dysfunctionassociated steatohepatitis (MASH). Here, the authors show that lanifibranor improves cardiometabolic health - insulin sensitivity, lipid and glucose metabolism, systemic inflammation and hepatic steatosis.

Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating/drinking behavior via FGF receptor 1/Klothoβ (FGFR1/KLB) complexes expressed in adipocytes, pancreatic acinar cells, and the nervous system in mice. Chronic administration of recombinant FGF21 or engineered variants improves metabolic health in rodents, nonhuman primates, and humans; however, the rapid turnover of these molecules limits therapeutic utility. Here we show that the bispecific anti-FGFR1/KLB agonist antibody BFKB8488A induced marked weight loss in obese cynomolgus monkeys while elevating serum adiponectin and the adipose expression of FGFR1 target genes, demonstrating its action as an FGF21 mimetic. In a randomized, placebo-controlled, single ascending-dose study in overweight/obese human participants, subcutaneous BFKB8488A injection caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that specific activation of the FGFR1/KLB complex in humans can be used as therapy for obesity-related metabolic defects.

Purpose We investigate the effects of 12-week interval training of moderate- or high-intensity exercise on blood lipids and plasma levels of adiponectin. Methods Thirty-four obese adolescent females [age = 15.9 ± 0.3 years; BMI and BMI- Z -score = 30.8 ± 1.6 kg/m 2 and 3 ± 0.3, respectively], were randomized to high-intensity interval training (HIIT, n  = 11), moderate-intensity interval training (MIIT, n  = 11), or a control group (CG, n  = 12). Maximal oxygen uptake ( V . O 2 peak ), maximal aerobic speed (MAS), plasma lipids and adiponectin levels were measured in all subjects before and after training. Results Following the training program, in both training groups, body mass, BMI- Z -score, and percentage body fat (% BF) decreased, while V . O 2 peak and MAS increased. Low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and adiponectin levels were positively altered (−12.6 and −7.4 %; 6.3 and 8.0 %; 35.8 and 16.2 %; high to moderate training program, respectively). Waist circumference, triglyceride and total cholesterol decreased only in HIIT group (−3.5; −5.3 and −7.0 %, respectively, in all P  < 0.05). Significant decrease in the usual index of insulin resistance (HOMA-IR) occurred in HIIT and MIIT groups (−29.2 ± 5.3 and −18.4 ± 8.6 %, respectively; P  < 0.01). Conclusion The results show that HIIT positively changes blood lipids and adiponectin variables in obese adolescent girls, resulting in improved insulin sensitivity, as attested by a lower HOMA-IR, and achieving better results compared to moderate-intensity exercise.

The present study aimed to investigate the serum levels of adiponectin (APN) and adiponectin receptor 1 (AdipoR1) in patients with type 2 diabetes mellitus (T2DM) combined with macrovascular complications (MVC), as well as their correlation with clinical parameters. A total of 60 T2DM patients were divided into 2 groups according to the presence of MVC: T2DM + MVC group (n=30) and T2DM group (n=30). Additionally, 30 healthy people were selected as control group (NC group). Clinical data and biological parameters were detected and recorded. T test was performed to compare the differences between two groups, and the results were corrected using Bonferroni method. Meanwhile, the correlation analysis and multiple stepwise regression analysis were used to analyze the association of APN and AdipoR1 with clinical factors. The levels of APN and AdipoR1 were significantly decreased in T2DM group and T2DM + MVC group compared with NC group, with the lowest value in T2DM + MVC group (all P<0.01). Serum APN levels were positively correlated with FINS and TG (r = 0.412, 0.316, respectively; both P<0.05), and negatively correlated with SBP, DBP and LDL-C (r = -0.292, -0.383, -0.334, respectively; all P<0.05). Serum levels of AdipoR1 were positively correlated with APN (r = 0.726, P<0.01), and negatively correlated with BMI, SBP, DBP, FBG, TC and LDL-C (r = -0.440, -0.446, -0.374, -0.444, -0.344, -0.709, respectively; all P<0.01). Serum levels of APN and AdipoR1 are significantly lower in T2DM group and T2DM + MVC group, showing lowest value in T2DM + MVC group. APN and AdipoR1 levels may influence glucose and lipid metabolism in T2DM patients.

BACKGROUND: Alternate day fasting (ADF; ad libitum “feed day”, alternated with 25% energy intake “fast day”), is effective for weight loss and cardio-protection in obese individuals. Whether these effects occur in normal weight and overweight individuals remains unknown. This study examined the effect of ADF on body weight and coronary heart disease risk in non-obese subjects. METHODS: Thirty-two subjects (BMI 20–29.9 kg/m²) were randomized to either an ADF group or a control group for 12 weeks. RESULTS: Body weight decreased (P < 0.001) by 5.2 ± 0.9 kg (6.5 ± 1.0%) in the ADF group, relative to the control group, by week 12. Fat mass was reduced (P < 0.001) by 3.6 ± 0.7 kg, and fat free mass did not change, versus controls. Triacylglycerol concentrations decreased (20 ± 8%, P < 0.05) and LDL particle size increased (4 ± 1 , P < 0.01) in the ADF group relative to controls. CRP decreased (13 ± 17%, P < 0.05) in the ADF group relative to controls at week 12. Plasma adiponectin increased (6 ± 10%, P < 0.01) while leptin decreased (40 ± 7%, P < 0.05) in the ADF group versus controls by the end of the study. LDL cholesterol, HDL cholesterol, homocysteine and resistin concentrations remained unchanged after 12 weeks of treatment. CONCLUSION: These findings suggest that ADF is effective for weight loss and cardio-protection in normal weight and overweight adults, though further research implementing larger sample sizes is required before solid conclusion can be reached.

Previous experimental studies have suggested curcumin as a safe phytochemical that can improve insulin resistance through effects on adiponectin and leptin. This study aimed to investigate the effect of curcumin on circulating adiponectin and leptin concentrations in patients with metabolic syndrome. In this pilot, randomized, double-blind, placebo-controlled trial, subjects who met the criteria of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria were randomly assigned to curcumin (n = 59; 1000 mg/d) or a placebo (n = 58) for 8 wk. Serum adiponectin and leptin concentrations were determined before and after intervention. The pooled effect size for the impact of curcumin supplementation on serum adiponectin and leptin levels was also estimated using random-effects metaanalysis. Eight-week supplementation with curcumin was associated with a significant increase in serum adiponectin levels (P < 0.001) and a reduction in serum leptin concentrations (P < 0.001). Serum leptin:adiponectin ratio was also improved by curcumin (P < 0.001). These beneficial effects of curcumin remained significant after adjustment for changes in serum lipids and glucose concentrations and baseline differences in body mass index and serum levels of glucose and glycated hemoglobin as potential confounders of treatment response. Metaanalysis suggested that curcumin supplementation can increase adiponectin levels by 76.78% (95% CI: 6.14–147.42; P = 0.0330), and reduce leptin by 26.49% (95% CI: −70.44 to 17.46), however this latter effect size did not reach statistical significance (P = 0.238). Curcumin can improve serum levels of adiponectin and leptin in patients with metabolic syndrome. This trial was registered at the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/) under Trial No. UMIN000018339. •Curcumin is a phytochemical with several cardiometabolic benefits.•The effect of curcumin on serum adiponectin and leptin levels was investigated in patients with metabolic syndrome.•After 8 wk of supplementation, curcumin was found to increase serum adiponectin levels.•Serum leptin and leptin:adiponectin ratio were decreased within the same period.•Improvement of circulating adipokines levels may justify the insulin-sensitizing effects of curcumin.

Abstract Background The adiponectin is one of the rare adipokines down-regulated with obesity and protects against obesity-related disorders. Similarly, the apolipoprotein M (apoM) is expressed in adipocytes and its expression in adipose tissue is associated with metabolic health. We compared circulating apoM with adiponectin regarding their relationship with metabolic parameters and insulin sensitivity and examined their gene expression patterns in adipocytes and in the adipose tissue. Methods Circulating apoM and adiponectin were examined in 169 men with overweight in a cross-sectional study, and 13 patients with obesity during a surgery-induced slimming program. Correlations with clinical parameters including the insulin resistance index (HOMA-IR) were analyzed. Multiple regression analyses were performed on HOMA-IR. The APOM and ADIPOQ gene expression were measured in the adipose tissue from 267 individuals with obesity and a human adipocyte cell line. Results Participants with type 2 diabetes had lower circulating adiponectin and apoM, while apoM was higher in individuals with dyslipidemia. Similar to adiponectin, apoM showed negative associations with HOMA-IR and hs-CRP (r < −0.2), and positive correlations with HDL markers (HDL-C and apoA-I, r > 0.3). Unlike adiponectin, apoM was positively associated with LDL markers (LDL-C and apoB100, r < 0.20) and negatively correlated with insulin and age (r < −0.2). The apoM was the sole negative determinant of HOMA-IR in multiple regression models, while adiponectin not contributing significantly. After surgery, the change in HOMA-IR was negatively associated with the change in circulating apoM (r = −0.71), but not with the change in adiponectin. The APOM and ADIPOQ gene expression positively correlated in adipose tissue (r > 0.44) as well as in adipocytes (r > 0.81). In adipocytes, APOM was downregulated by inflammatory factors and upregulated by adiponectin. Conclusions The apoM rises as a new partner of adiponectin regarding insulin sensitivity. At the adipose tissue level, the adiponectin may be supported by apoM to promote a healthy adipose tissue. Trial registration NCT01277068, registered 13 January 2011; NCT02332434, registered 5 January 2015; and NCT00390637, registered 20 October 2006.

Background Type 2 diabetes mellitus (T2DM) is a chronic condition characterized by insulin resistance and impaired insulin production, leading to elevated blood glucose levels. Curcumin, a polyphenolic compound from Curcuma longa, has shown potential in improving insulin sensitivity and reducing blood glucose levels, which may help mitigate type 2 diabetes progression. Objective To assess the efficacy of improving type 2 diabetes (T2DM). Study design This randomized, double-blind, placebo-controlled trial included subjects ( n  = 272) with criteria for type 2 diabetes. Methods All subjects were randomly assigned to receive curcumin (1500 mg/day) or placebo with blind labels for 12 months. To assess the improvement of T2DM after curcumin treatments body weight and body mass index, fasting plasma glucose, glycosylated hemoglobin A 1c, β-cell function (homeostasis model assessment [HOMA-β]), insulin resistance (HOMA-IR), insulin, adiponectin, and leptin were monitored at the baseline and at 3-, 6-, 9-, and 12-month visits during the course of intervention. Results After 12 months of treatment, the curcumin-treated group showed a significant decrease in fasting blood glucose (115.49 vs.130.71; P  < 0.05), HbA 1c (6.12 vs. 6.47; P  < 0.05). In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (136.20 vs. 105.19; P  < 0.01) The curcumin-treated group showed a lower level of HOMA-IR (4.86 vs. 6.04; P  < 0.001) and higher adiponectin (14.51 vs. 10.36; P  < 0.001) when compared to the placebo group. The curcumin-treated group also showed a lower level of leptin (9.42 vs. 20.66; P  < 0.001). Additionally, body mass index was lowered (25.9 4 vs.29.34), with a P value of 0.001. Conclusions A 12-month curcumin intervention in type 2 diabetes patients shows a significant glucose-lowering effect. Curcumin treatment appeared to improve the overall function of β-cells and reduce both insulin resistance and body weight, with very minor adverse effects. Curcumin intervention in obese patients with type 2 diabetes may be beneficial. Trial registration Thai clinical trials regentrify no.20140303003.

•A fructose-rich single meal leads to increased triglyceride and leukocyte levels.•A fructose overload in a typical meal does not affect systemic cytokine levels.•Intake of high-fructose meals potentializes inflammatory and metabolic dysfunction. We aimed to evaluate the acute effect of a fructose-rich single meal on metabolic and inflammatory biomarkers This single-center, double-masked, randomized crossover trial recruited females aged 20 to 47 with a normal body mass index and was conducted at Hospital das Clínicas (Belo Horizonte, MG, Brazil). Participants received a standardized meal with either sucrose, glucose, or a fructose overload. Blood samples were collected after overnight fasting (baseline) and at 30, 60, 120, and 240 minutes postprandial. Serum levels of glucose, triglycerides (primary outcome), total cholesterol, alanine aminotransferase, aspartate aminotransferase, adiponectin, leptin, resistin, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-17, interferon-gamma, tumor necrosis factor, eotaxin, and total blood leukocytes were measured. This trial was completed with 25 enrolled participants, and three dropped out. The per-protocol analysis included 22 participants. As expected, postprandial glycemia increased 30 minutes after consuming meals rich in sucrose (P = 0.045) or glucose (P < 0.001). Triglyceride and leucocyte concentrations increased only at 240 minutes after consuming a high-fructose meal (P < 0.05). Regardless of the type of carbohydrate overload, leptin concentrations decreased postprandially compared to baseline at all time points (P < 0.05). Four participants reported adverse events after consuming the standardized meal with glucose or fructose, including nausea and malaise. Our findings indicate that a fructose-rich single meal leads to a more significant increase in triglyceride and leukocyte concentrations compared to glucose and sucrose in healthy women. These findings support concerns regarding the potential inflammatory and metabolic dysfunction associated with frequent consumption of high-fructose meals.

Depression is the most devastating mental disorder and one of the leading contributors to the global medical burden. Current antidepressant prescriptions present drawbacks, including treatment resistance, delayed onset of treatment response, and side effects. The rapid and long-lasting antidepressant effect of ketamine has brought hope to treatment-resistant major depressive disorder patients. However, ketamine has undesirable addictive properties and is a drug of abuse. There is an urgent need, therefore, to develop novel pharmacological interventions that could be as effective as ketamine, but without its side effects. Adiponectin, a pleiotropic adipocyte-secreted hormone, has insulin-sensitizing and neurotrophic properties. It can cross the blood-brain barrier and target multiple brain regions where the adiponectin receptors are detected. Emerging evidence has suggested that adiponectin and the adiponectin receptor agonist, AdipoRon, could promote adult neurogenesis, dendritic and spine remodeling, and synaptic plasticity in the hippocampus, resulting in antidepressant effects in adult mice. By summarizing the most recent clinical and animal studies, this review provides a timely insight on how modulating the adiponergic system in the hippocampus could be a potential therapeutic target for an effective and fast-acting antidepressant response.