title: Hypothalamic malonyl-CoA and the control of food intake.
abstract: 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.
authors.affiliation: Department of Metabolism and Aging, Scripps Research Institute, Jupiter, FL 33458, USA. Electronic address: sgao@scripps.edu.
authors.forename: Su
authors.initials: S
authors.lastname: Gao
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Moran
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Butler
mesh_terms: D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004435:Eating / Q000502:physiology*; D005215:Fasting / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D008316:Malonyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase
keywords: Carnitine palmitoyltransferase; Fatty acid; Food intake; Hypothalamus; Malonyl-CoA