Hypothalamic malonyl-CoA and the control of food intake

PHYSIOLOGY & BEHAVIOR

卷:122

Review

Gao, Su¹  Moran, Timothy H.²  Lopaschuk, Gary D.³  Butler, Andrew A.¹ 

[1] Scripps Res Inst, Dept Metab & Aging, Jupiter, FL 33458 USA

[2] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA

[3] Univ Alberta, Dept Pediat, Edmonton, AB T6G 2S2, Canada

关键词: Hypothalamus;    Food intake;    Malonyl-CoA;    Carnitine palmitoyltransferase;    Fatty acid;   

DOI  :  10.1016/j.physbeh.2013.07.014

来源: Elsevier

【 摘 要 】

Fatty acid metabolism is implicated in the hypothalamic control of food intake. In this regard, malonyl-CoA, an intermediate in fatty acid synthesis, is emerging as a key player. Malonyl-CoA in the hypothalamus has been proposed as an anorectic mediator in the central control of feeding. A large body of evidence demonstrates that modulating hypothalamic activities of malonyl-CoA metabolic enzymes impacts food intake. Malonyl-CoA action appears to play a significant role in the intracellular signaling pathways underlying leptin anorectic effect in the arcuate nucleus. Ghrelin's hypothalamic effect on feeding may also involve the change in malonyl-CoA metabolism. Hypothalamic malonyl-CoA levels are altered in response to fasting and refeeding, suggesting physiological relevance of the changes in malonyl-CoA level in the controls of feeding and energy balance. Malonyl-CoA inhibits the acyltransferase activity of carnitine palmitoyltransferase-1 (CPT-1), and CPT-1 was considered as a downstream effector in hypothalamic malonyl-CoA effect on feeding. However, recent evidence has not been entirely consistent with this notion. In the arcuate nucleus, the inhibition of CPT-1 acyltransferase activity does not play an important role in the feeding effect of either leptin or cerulenin (a fatty acid synthase inhibitor) that requires the increase in malonyl-CoA level. Alternatively, the brain isoform of CPT-1 (CPT-1c) may act as a downstream target in the malonyl-CoA signaling pathways. CPT-1c does not possess a typical acyltransferase activity, and the exact molecular function of this protein is currently unknown. Recent data indicate it is involved in ceramide metabolism. Of relevance, in the arcuate nucleus, CPT-1c may link malonyl-CoA to ceramide metabolism to affect food intake. (C) 2013 Elsevier Inc. All rights reserved.

【 授权许可】

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