Isocitrate dehydrogenase 2 protects mice from high-fat diet-induced metabolic stress by limiting oxidative damage to the mitochondria from brown adipose tissue

Younghoon GoDo-Young KimSun Hee LeeOk-Hee KimYong Hyun JeonTaeg Kyu KwonJae-Hoon BaeDae-Kyu SongIm Joo RhyuIn-Kyu LeeJae-Ho LeeMinho ShongByung-Chul OhChristopher PetucciJeen-Woo ParkTimothy F. OsborneSeung-Soon Im
Dept. of Anatomy (해부학); Dept. of Physiology (생리학)
Issue Date
Experimental and Molecular Medicine, Vol.52(2) : 238-252, 2020
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.
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1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Anatomy (해부학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
Keimyung Author(s)
이재호; 배재훈; 송대규; 임승순
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