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KMID : 0620920200520020001
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Experimental & Molecular Medicine
2020 Volume.52 No. 2 p.1 ~ p.1
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Isocitrate dehydrogenase 2 protects mice from high-fat diet-induced metabolic stress by limiting oxidative damage to the mitochondria from brown adipose tissue
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Lee Jae-Ho
Go Young-Hoon
Kim Do-Young
Lee Sun-Hee
Kim Ok-Hee
Jeon Yong-Hyun
Kwon Taeg-Kyu
Bae Jae-Hoon
Song Dae-Kyu
Rhyu Im-Joo
Lee In-Kyu
Shong Min-Ho
Oh Byung-Chul
Petucci Christopher
Park Jeen-Woo
Osborne Timothy F.
Im Seung-Soon
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Abstract
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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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KEYWORD
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Metabolic syndrome, Obesity
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