Ketone body metabolism and cardiovascular disease

被引:333
作者
Cotter, David G. [1 ,2 ]
Schugar, Rebecca C. [1 ]
Crawford, Peter A. [1 ,3 ]
机构
[1] Washington Univ, Cardiovasc Res Ctr, Dept Med, St Louis, MO 63110 USA
[2] Washington Univ, Dept Pediat, St Louis, MO 63110 USA
[3] Washington Univ, Dept Genet, St Louis, MO 63110 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2013年 / 304卷 / 08期
基金
美国国家卫生研究院;
关键词
mitochondrial function; substrate competition; HMGCS2; CoA transferase/SCOT; lipogenesis; ACETOACETYL-COA SYNTHETASE; MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL-COA SYNTHASE; FATTY-ACID-METABOLISM; DIET-INDUCED OBESITY; COENZYME-A-TRANSFERASE; GUT MICROBIOTA; BETA-HYDROXYBUTYRATE; RAT-HEART; KETOGENIC DIET; SUCCINYL-COA;
D O I
10.1152/ajpheart.00646.2012
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cotter DG, Schugar RC, Crawford PA. Ketone body metabolism and cardiovascular disease. Am J Physiol Heart Circ Physiol 304: H1060-H1076, 2013. First published February 8, 2013; doi: 10.1152/ajpheart.00646.2012.-Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, beta-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states.
引用
收藏
页码:H1060 / H1076
页数:17
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