Blockade of interleukin 6 signalling ameliorates systemic insulin resistance through upregulation of glucose uptake in skeletal muscle and improves hepatic steatosis in high-fat diet fed mice.

Mice fed high-fat diet (HFD) demonstrate obesity-related systemic insulin resistance (IR). Aim of this study is to clarify the role of interleukin (IL)-6 in IR in vivo focusing on skeletal muscle, adipose tissue and liver. Plasma markers of IR and hepatic IL-6 signalling were examined in eight-week HFD feeding C57/BL6 mice. Furthermore, IR-related molecules in skeletal muscles, adipose tissues and livers were investigated following a single injection of anti- IL-6 receptor neutralizing antibody (MR16-1) in two-week HFD feeding mice. To investigate the role of IL-6 in hepatic steatosis by prolonged HFD, hepatic triglyceride accumulation was assessed in eight-week HFD feeding mice with continuous MR16-1 treatment. High-fat diet for both 2 and 8 weeks elevated plasma IL-6, insulin and leptin, which were decreased by MR16-1 treatment. A single injection of MR16-1 ameliorated IR as assessed by glucose and insulin tolerance test, which may be attributable to upregulation of glucose transporter type 4 via phosphorylation of AMP-activated protein kinase as well as upregulation of peroxisome proliferator-activated receptor alpha in livers and, particularly, in skeletal muscles. MR16-1 also decreased mRNA expression of leptin and tumour necrosis factor-alpha and increased that of adiponectin in adipose tissue. High-fat diet for 8 weeks, not 2 weeks, induced hepatic steatosis and increased hepatic triglyceride content, all of which were ameliorated by MR16-1 treatment. Blockade of excessive IL-6 stimulus ameliorated HFD-induced IR in a skeletal muscle and modulated the production of adipokines from an early stage of NAFLD, leading to prevention of liver steatosis for a long term.

Yamaguchi K ，Nishimura T ，Ishiba H ，Seko Y ，Okajima A ，Fujii H ，Tochiki N ，Umemura A ，Moriguchi M ，Sumida Y ，Mitsuyoshi H ，Yasui K ，Minami M ，Okanoue T ，Itoh Y ... -  《-》

Piperine reverses high fat diet-induced hepatic steatosis and insulin resistance in mice.

This study examined the effect of piperine on hepatic steatosis and insulin resistance induced in mice by feeding a high-fat diet (HFD) for 13 weeks and elucidated potential underlying molecular mechanisms. Administration of piperine (50 mg/kg body weight) to mice with HFD-induced hepatic steatosis resulted in a significant increase in plasma adiponectin levels. Also, elevated plasma concentrations of insulin and glucose and hepatic lipid levels induced by feeding a HFD were reversed in mice when they were administered piperine. However, piperine did not reduce body weight and other biochemical markers to an extent where they became equal to the levels found in the CD-fed mice. Piperine reversed HFD-induced down-regulation of adiponecitn-AMP-activated protein kinase (AMPK) signalling molecules which play an important role in mediating lipogenesis, fatty acid oxidation and insulin signalling in the livers of mice. The expressions of lipogenic target genes were decreased, whereas the expression of carnitine palmitoyltransferase 1 (CPT1) gene involved in fatty acid oxidation was increased in the livers of the Pin50 group. Piperine significantly decreased the phosphorylation of insulin receptor substrate-1 (IRS-1) compared with the HFD-fed mice. Administration of piperine appeared to reverse preexisting HFD-induced hepatic steatosis and insulin resistance, probably by activation of adiponectin-AMPK signalling in mice.

Choi S ，Choi Y ，Choi Y ，Kim S ，Jang J ，Park T ... -  《-》

Long-term intake of rice improves insulin sensitivity in mice fed a high-fat diet.

The aim of this study was to evaluate the effects of rice as a carbohydrate source and its molecular mechanisms on insulin resistance induced by a high-fat diet (HFD). C57 BL/6 J mice were divided into three groups and were fed a low-fat diet (LFD); a HFD (with 18% fat, 0.5% cholesterol, 51.5% w/w cornstarch and sucrose); or a HFD with rice (HFD-CR, with 18% fat, 0.5% cholesterol and 51.5% w/w rice powder) for 12 wk. In the HFD-CR diet, cooked rice powder was substituted for cornstarch and sucrose in the HFD as a carbohydrate source. HFD-CR-fed mice had significantly lower body weight, blood glucose, insulin and leptin levels and ameliorated glucose responses with decreased homeostasis model assessment-insulin resistance compared with HFD-fed mice. Hepatic mRNA levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were down-regulated in the HFD-CR group. The hypertrophied islet size and the decreased pancreatic mRNA expression of glucose transporter 2 in the HFD group were normalized with cooked rice consumption. Rice promoted glucose uptake by activating AMP-activated protein kinase and downstream glucose transporter 4 in the skeletal muscle. Rice consumption as a carbohydrate source might potentiate improvements in glucose uptake via AMP-activated protein kinase activation and glucose transporter 4 expression in the skeletal muscles, thereby improving insulin sensitivity.

Choi WH ，Um MY ，Ahn J ，Jung CH ，Ha TY ... -  《-》

Ergostatrien-3β-ol from Antrodia camphorata inhibits diabetes and hyperlipidemia in high-fat-diet treated mice via regulation of hepatic related genes, glucose transporter 4, and AMP-activated protein kinase phosphorylation.

Kuo YH ，Lin CH ，Shih CC 《-》

Soy β-conglycinin improves glucose uptake in skeletal muscle and ameliorates hepatic insulin resistance in Goto-Kakizaki rats.

Although the underlying mechanism is unclear, β-conglycinin (βCG), the major component of soy proteins, regulates blood glucose levels. Here, we hypothesized that consumption of βCG would normalize blood glucose levels by ameliorating insulin resistance and stimulating glucose uptake in skeletal muscles. To test our hypothesis, we investigated the antidiabetic action of βCG in spontaneously diabetic Goto-Kakizaki (GK) rats. Our results revealed that plasma adiponectin levels and adiponectin receptor 1 messenger RNA expression in skeletal muscle were higher in βCG-fed rats than in casein-fed rats. Phosphorylation of adenosine monophosphate-activated protein kinase (AMP kinase) but not phosphatidylinositol-3 kinase was activated in βCG-fed GK rats. Subsequently, βCG increased translocation of glucose transporter 4 to the plasma membrane. Unlike the results in skeletal muscle, the increase in adiponectin receptor 1 did not lead to AMP kinase activation in the liver of βCG-fed rats. The down-regulation of sterol regulatory element-binding factor 1, which is induced by low insulin levels, promoted the increase in hepatic insulin receptor substrate 2 expression. Based on these findings, we concluded that consumption of soy βCG improves glucose uptake in skeletal muscle via AMP kinase activation and ameliorates hepatic insulin resistance and that these actions may help normalize blood glucose levels in GK rats.

Tachibana N ，Yamashita Y ，Nagata M ，Wanezaki S ，Ashida H ，Horio F ，Kohno M ... -  《-》