잠시만 기다려 주세요. 로딩중입니다.

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

Experimental & Molecular Medicine 2020년 52권 2호 p.1 ~ 1
이제호 ( Lee Jae-Ho ) - Keimyung University School of Medicine Department of Physiology

 ( Go Young-Hoon ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Internal Medicine
 ( Kim Do-Young ) - Keimyung University School of Medicine Department of Physiology
 ( Lee Sun-Hee ) - Keimyung University School of Medicine Department of Physiology
김옥희 ( Kim Ok-Hee ) - Gachon University School of Medicine Department of Physiology
 ( Jeon Yong-Hyun ) - Daegu-Gyeongbuk Medical Innovation Foundation Laboratory Animal Center
권택규 ( Kwon Taeg-Kyu ) - Keimyung University School of Medicine Department of Immunology
배재훈 ( Bae Jae-Hoon ) - Keimyung University School of Medicine Department of Physiology
송대규 ( Song Dae-Kyu ) - Keimyung University School of Medicine Department of Physiology
류임주 ( Rhyu Im-Joo ) - Korea University College of Medicine Department of Anatomy
이인규 ( Lee In-Kyu ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Internal Medicine
송민호 ( Shong Min-Ho ) - Chungnam National University Hospital Research Center for Endocrinology and Metabolism
오병철 ( Oh Byung-Chul ) - Gachon University School of Medicine Department of Physiology
 ( Petucci Christopher ) - Sanford Burnham Prebys Medical Discovery Institute Center for Metabolic Origins of Disease
박진우 ( Park Jeen-Woo ) - Kyungpook National University College of Natural Sciences School of Life Science and Biotechnology
 ( Osborne Timothy F. ) - Johns Hopkins University School of Medicine Department of Medicine
 ( Im Seung-Soon ) - Keimyung University School of Medicine Department of Physiology

Abstract


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.

키워드

Metabolic syndrome; Obesity
원문 및 링크아웃 정보
 
등재저널 정보
SCI(E)
MEDLINE
KCI
KoreaMed
KAMS