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Jae-Ho Lee,고영훈,Do-Young Kim,Sun Hee Lee,김옥희,Yong Hyun Jeon,권택규,Jae-Hoon Bae,Dae Kyu Song,Im Joo Rhyu,In-Kyu Lee,송민호,오병철,Christopher Petucci,Jeen-Woo Park,Timothy F. Osborne,임승순 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
Isocitrate dehydrogenase 2 (IDH2) is an NADP+-dependent enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate in the mitochondrial matrix, and is critical for the production of NADPH to limit the accumulation of mitochondrial reactive oxygen species (ROS). Here, we showed that high-fat diet (HFD) feeding resulted in accelerated weight gain in the IDH2KO mice due to a reduction in whole-body energy expenditure. Moreover, the levels of NADP+, NADPH, NAD+, and NADH were significantly decreased in the brown adipose tissue (BAT) of the HFD-fed IDH2KO animals, accompanied by decreased mitochondrial function and reduced expression of key genes involved in mitochondrial biogenesis, energy expenditure, and ROS resolution. Interestingly, these changes were partially reversed when the antioxidant butylated hydroxyanisole was added to the HFD. These observations reveal a crucial role for IDH2 in limiting ROS-dependent mitochondrial damage when BAT metabolism is normally enhanced to limit weight gain in response to dietary caloric overload.