medric medric
[닫기]
잠시만 기다려 주세요. 로딩중입니다.

Therapeutic effect of dichloroacetate against atherosclerosis via hepatic FGF21 induction mediated by acute AMPK activation

Experimental & Molecular Medicine 2019년 51권 9호 p.114 ~ 114
 ( Min Byong-Keol ) - Kyungpook National University Department of Biomedical Science

 ( Oh Chang-Joo ) - Kyungpook National University Research Institute of Aging and Metabolism
 ( Park Sung-Mi ) - Kyungpook National University Hospital Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease
 ( Lee Ji-Min ) - Kyungpook National University Department of Biomedical Science
 ( Go Young-Hoon ) - Korea Institute of Oriental Medicine Korean Medicine Application Center
 ( Park Bo-Yoon ) - Kyungpook National University Department of Biomedical Science
 ( Kang Hyeon-Ji ) - Kyungpook National University Research Institute of Aging and Metabolism
 ( Kim Dong-Wook ) - Kyungpook National University Hospital Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease
 ( Kim Jeong-Eun ) - Kyungpook National University Hospital Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease
 ( Yoo Eun-Kyung ) - Kyungpook National University Hospital Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease
 ( Kim Hui-Eon ) - Kyungpook National University Hospital Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease
 ( Kim Mi-Jin ) - Kyungpook National University Research Institute of Aging and Metabolism
 ( Jeon Yong-Hyun ) - Daegu-Gyeongbuk Medical Innovation Foundation Laboratory Animal Center
 ( Kim Yong-Hoon ) - Korea Research Institute of Bioscience and Biotechnology Laboratory Animal Resource Center
 ( Lee Chul-Ho ) - Korea Research Institute of Bioscience and Biotechnology Laboratory Animal Resource Center
 ( Jeon Jae-Han ) - Kyungpook National University Hospital Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease
 ( Lee In-Kyu ) - Kyungpook National University School of Medicine Department of Internal Medicine

Abstract


Dyslipidemia-induced atherosclerosis, which has a risk of high morbidity and mortality, can be alleviated by metabolic activation associated with mitochondrial function. The effect of dichloroacetate (DCA), a general pyruvate dehydrogenase kinase (PDK) inhibitor, on in vivo energy expenditure in ApoE?/? mice fed a western diet (WD) has not yet been investigated. WD-fed ApoE?/? mice developed atherosclerotic plaques and hyperlipidemia along with obesity, which were significantly ameliorated by DCA administration. Increased oxygen consumption was associated with heat production in the DCA-treated group, with no change in food intake or physical activity compared with those of the control. These processes were correlated with the increased gene expression of Dio2 and Ucp-1, which represents brown adipose tissue (BAT) activation, in both WD-induced atherosclerosis and high-fat-induced obesity models. In addition, we found that DCA stimulated hepatic fibroblast growth factor 21 (Fgf21) mRNA expression, which might be important for lowering lipid levels and insulin sensitization via BAT activation, in a dose- and time-dependent manner associated with serum FGF21 levels. Interestingly, Fgf21 mRNA expression was mediated in an AMP-activated protein kinase (AMPK)-dependent manner within several minutes after DCA treatment independent of peroxisome proliferator-activated receptor alpha (PPARα). Taken together, the results suggest that enhanced glucose oxidation by DCA protects against atherosclerosis by inducing hepatic FGF21 expression and BAT activation, resulting in augmented energy expenditure for heat generation.

키워드

Atherosclerosis; Dyslipidaemias
원문 및 링크아웃 정보
 
등재저널 정보