Melinjo (Gnetum gnemon L.) seed extract induces uncoupling protein 1 expression in brown fat and protects mice against diet-induced obesity, inflammation, and insulin resistance.

Dietary supplementation with melinjo (Gnetum gnemon L.) seed extract (MSE) has been proposed as an anti-obesity strategy. However, it remains unclear how MSE modulates energy balance. We tested the hypothesis that dietary MSE reduces energy intake and/or increases physical activity and metabolic thermogenesis in brown and white adipose tissue (BAT and WAT) in mice. Twenty-four C57BL/6 J mice were provided with normal diet, high-fat diet (HFD), or HFD with 1% MSE added, for 17 weeks. Food intake, spontaneous locomotor activity, hepatic triglyceride (TG) content, and blood parameters were examined. Mitochondrial thermogenesis-associated molecule and inflammatory marker expression levels in BAT and WAT were examined by quantitative PCR and western blotting. Dietary MSE did not affect energy intake or spontaneous locomotor activity, but significantly suppressed HFD-induced fat accumulation, hyperglycemia, and hyperinsulinemia. Homeostasis model assessment of insulin resistance score and hepatic TG content were both lower in the MSE-supplemented HFD-fed group than in the HFD-fed group, indicating reduced insulin resistance and a less fatty liver. Dietary MSE upregulated thermogenic uncoupling protein 1 (UCP1) and mitochondrial marker cytochrome c oxidase subunit IV protein expression in BAT; this was closely associated with sirtuin 1 mRNA induction. mRNAs of adipose inflammatory markers, such as monocyte chemotactic 1 and interleukin-1, were induced by HFD but suppressed by MSE. Considering that UCP1 protein expression is the most physiologically relevant parameter to assess the thermogenic capacities of BAT, our results indicate that dietary MSE supplementation induces BAT thermogenesis and reduces obesity-associated adipose tissue inflammation, hepatic steatosis, and insulin resistance.

Royal jelly ameliorates diet-induced obesity and glucose intolerance by promoting brown adipose tissue thermogenesis in mice.

INTRODUCTION: Identification of thermogenic food ingredients is potentially a useful strategy for the prevention of obesity and related metabolic disorders. It has been reported that royal jelly (RJ) supplementation improves insulin sensitivity; however, its impacts on energy expenditure and adiposity remain elusive. We investigated anti-obesity effects of RJ supplementation and their relation to physical activity levels and thermogenic capacities of brown (BAT) and white adipose tissue (WAT). METHODS: C57BL/6J mice were fed under four different experimental conditions for 17 weeks: normal diet (ND), high fat diet (HFD), HFD with 5% RJ, and HFD with 5% honey bee larva powder (BL). Spontaneous locomotor activity, hepatic triglyceride (TG) content, and blood parameters were examined. Gene and protein expressions of thermogenic uncoupling protein 1 (UCP1) and mitochondrial cytochrome c oxidase subunit IV (COX-IV) in BAT and WAT were investigated by qPCR and Western blotting analysis, respectively. RESULTS: Dietary RJ, but not BL, suppressed HFD-induced accumulations of WAT and hepatic TG without modifying food intake. Consistently, RJ improved hyperglycemia and the homeostasis model assessment-insulin resistance (HOMA-IR). Although dietary RJ and BL unchanged locomotor activity, gene and protein expressions of UCP1 and COX-IV in BAT were increased in the RJ group compared to the other experimental groups. Neither the RJ nor BL treatment induced browning of WAT. CONCLUSION: Our results indicate that dietary RJ ameliorates diet-induced obesity, hyperglycemia, and hepatic steatosis by promoting metabolic thermogenesis in BAT in mice. RJ may be a novel promising food ingredient to combat obesity and metabolic disorders.

Adiponectin Inhibits LPS-Induced HMGB1 Release through an AMP Kinase and Heme Oxygenase-1-Dependent Pathway in RAW 264 Macrophage Cells.

High mobility group protein B1 (HMGB1) is a late inflammatory mediator that exaggerates septic symptoms. Adiponectin, an adipokine, has potent anti-inflammatory properties. However, possible effects of adiponectin on lipopolysaccharide- (LPS-) induced HMGB1 release are unknown. The aim of this study was to investigate effects of full length adiponectin on HMGB1 release in LPS-stimulated RAW 264 macrophage cells. Treatment of the cells with LPS alone significantly induced HMGB1 release associated with HMGB1 translocation from the nucleus to the cytosol. However, prior treatment with adiponectin suppressed LPS-induced HMGB1 release and translocation. The anti-inflammatory cytokine interleukin- (IL-) 10 similarly suppressed LPS-induced HMGB1 release. Adiponectin treatment decreased toll-like receptor 4 (TLR4) mRNA expression and increased heme oxygenase- (HO-) 1 mRNA expression without inducing IL-10 mRNA, while IL-10 treatment decreased TLR2 and HMGB1 mRNA expression and increased the expression of IL-10 and HO-1 mRNA. Treatment with the HO-1 inhibitor ZnPP completely prevented the suppression of HMGB1 release by adiponectin but only partially inhibited that induced by IL-10. Treatment with compound C, an AMP kinase (AMPK) inhibitor, abolished the increase in HO-1 expression and the suppression of HMGB1 release mediated by adiponectin. In conclusion, our results indicate that adiponectin suppresses HMGB1 release by LPS through an AMPK-mediated and HO-1-dependent IL-10-independent pathway.