Mice Deficient in the Respiratory Chain Gene Cox6a2 Are Protected against High-Fat Diet-Induced Obesity and Insulin Resistance
نویسندگان
چکیده
Oxidative phosphorylation in mitochondria is responsible for 90% of ATP synthesis in most cells. This essential housekeeping function is mediated by nuclear and mitochondrial genes encoding subunits of complex I to V of the respiratory chain. Although complex IV is the best studied of these complexes, the exact function of the striated muscle-specific subunit COX6A2 is still poorly understood. In this study, we show that Cox6a2-deficient mice are protected against high-fat diet-induced obesity, insulin resistance and glucose intolerance. This phenotype results from elevated energy expenditure and a skeletal muscle fiber type switch towards more oxidative fibers. At the molecular level we observe increased formation of reactive oxygen species, constitutive activation of AMP-activated protein kinase, and enhanced expression of uncoupling proteins. Our data indicate that COX6A2 is a regulator of respiratory uncoupling in muscle and we demonstrate that a novel and direct link exists between muscle respiratory chain activity and diet-induced obesity/insulin resistance.
منابع مشابه
Effects of Endurance Training on the Expression of Cathepsin B (CTSB) and Cathepsin L (CTSL) genes in the Adipose Tissue of Mice with a High-Fat Diet
Introduction: In high-fat diet-induced obesity, the levels of cathepsin L (CTSL) and cathepsin B (CTSB) increase in adipocytes, resulting in insulin resistance in the adipose tissue. In this study, the preventive effect of endurance training on the gene expression of CTSL and CTSB was investigated in the adipose tissue of mice with a high-fat diet. Materials and Methods: Twenty-one male mice (a...
متن کاملMomordica cymbalaria fruit extract attenuates high-fat diet-induced obesity and diabetes in C57BL/6 mice
Objective(s): The present study was aimed to evaluate the effect of methanolic fruit extract of Momordica cymbalaria (MeMC) against high-fat diet-induced obesity and diabetes in C57BL/7 mice.Materials and Methods: In the present study, six weeks old male C57BL/6 mice were divided into four groups. G-1 and G-2 served as lean control and HFD control, G-3 and G-4 received MeMC 25 and 50 mg/kg, BW ...
متن کاملThe effect of aerobic exercise on epicardial adipose tissue, insulin resistance, and some liver enzymes in high-fat diet-induced obesity male wistar rat
Background and Aim: Due to the prevalence and socio-economic consequences of obesity in mortality, cardiovascular (CAD) and nonalcoholic fatty liver disease the effectiveness of aerobic exercise on epicardial adipose tissue (EAT), insulin resistance (IR) and some liver enzymes of high-fat diet-induced obesity male wistar rats was investigated. Methods: Thirty-two male Wistar rats with an averag...
متن کاملThe effects of high fat diet-induced obesity and interval and continuous exercise training on visceral fat SIRT1 and insulin resistance in male rats
Introduction. The aim of this study was to investigate the effects of high fat diet-induced obesity and interval and continuous exercise training on visceral fat SIRT1 and insulin resistance in male rats. Method. Forty male rats were divided into two groups: high-fat diet (HFD; n=32) and standard diet (C; n=8). After 10 weeks inducing obesity, eight rats from the HFD and C groups were sacrifi...
متن کاملRole of muscle c-Jun NH2-terminal kinase 1 in obesity-induced insulin resistance.
Obesity caused by feeding of a high-fat diet (HFD) is associated with an increased activation of c-Jun NH(2)-terminal kinase 1 (JNK1). Activated JNK1 is implicated in the mechanism of obesity-induced insulin resistance and the development of metabolic syndrome and type 2 diabetes. Significantly, Jnk1(-)(/)(-) mice are protected against HFD-induced obesity and insulin resistance. Here we show th...
متن کامل