Regulation of energy expenditure by isocitrate dehydrogenase 2 on brown adipose tissue

Identification: Lee, Jae-ho


Regulation of energy expenditure by isocitrate dehydrogenase 2 on brown adipose tissue
Jae-ho Lee, Hye Suk Kang, Jae-Hoon Bae, Seung-Soon Im*
Department of Physiology, Keimyung University School of Medicine
Brown adipose tissue (BAT) is responsible for energy homeostasis and thermogenesis by enhancing its mitochondrial fatty acid oxidation (FAO). Increased oxidative stress in adipose tissue is an early instigator of obesity-associated metabolic syndrome. 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 α-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.
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2016R1A2B4008516).


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