* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Role of IDH2 in the brown adipose tissue Abstract
Survey
Document related concepts
Biochemistry wikipedia , lookup
Mitochondrial replacement therapy wikipedia , lookup
NADH:ubiquinone oxidoreductase (H+-translocating) wikipedia , lookup
Citric acid cycle wikipedia , lookup
Evolution of metal ions in biological systems wikipedia , lookup
Nicotinamide adenine dinucleotide wikipedia , lookup
Oxidative phosphorylation wikipedia , lookup
Fatty acid metabolism wikipedia , lookup
Mitochondrion wikipedia , lookup
Basal metabolic rate wikipedia , lookup
Transcript
Role of IDH2 in the brown adipose tissue Abstract Brown adipose tissue (BAT) plays a key role in controlling energy expenditure and thermogenesis by fatty acid oxidation (FAO) in mitochondria. Accumulation of oxidative stress in adipose tissue is one of the early events in the development of metabolic syndrome in obesity. Nonetheless, a cause and effect relationship between oxidative stress and obesity is not well understood. Isocitrate dehydrogenase 2 (IDH2) is a NADP+-dependent isocitrate dehydrogenase which is located in the mitochondria and catalyzes the oxidative decarboxylation of isocitrate to -ketoglutarate. Even though IDH2 is involved in intermediary metabolism and decrease of reactive oxygen species (ROS), there is currently a limited understanding of how IDH2 ameliorates ROS-based obesity at the molecular level. Here, we describe the function of IDH2 in high fat diet-induced obesity. IDH2 knockout (KO) mice showed reduction of energy expenditure and FAO, resulting in increase of fat mass. Moreover, IDH2 KO mice exhibited significantly elevated level of NADP+/NADPH as well as NAD+/NADH ratio in BAT. And ROS production was increased in IDH2 KO cells, suggesting that loss of IDH2 induces BAT dysfunction owing to inhibition of ROS-scavenging system. In summary, the present study showed that deficiency of IHD2 leads to mitochondrial dysfunction and increased ROS production, resulting in decrease of FAO and increase of energy imbalance. These data demonstrate a previously unrecognized contribution of IDH2 to ROS-mediated obesity.