Hypothalamic malonyl-coenzyme A and the control of energy balance.
An intermediate in the fatty acid biosynthetic pathway, malonyl-coenzyme A (CoA), has emerged as a major regulator of energy homeostasis not only in peripheral metabolic tissues but also in regions of the central nervous system that control satiety and energy expenditure. Fluctuations in hypothalamic malonyl-CoA lead to changes in food intake and peripheral energy expenditure in a manner consistent with an anorexigenic signaling intermediate. Hypothalamic malonyl-CoA is regulated by nutritional and endocrine cues including glucose and leptin, respectively. That malonyl-CoA is an essential component in the energy homeostatic signaling system of the hypothalamus is supported by convergence of physiological, pharmacological, and genetic evidence. This review will focus on evidence implicating malonyl-CoA as a central player in the control of body weight and adiposity as well as clues to the molecular mechanism by which carbon flux through the fatty acid biosynthetic pathway is linked to the neural control of energy balance.
Wolfgang
Michael J
MJ
Department of Biological Chemistry, Johns Hopkins University School of Medicine, 512 WBSB, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
Lane
M Daniel
MD
D050154:Adiposity / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism; D064429:Fatty Acid Synthases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction; D015398:Signal Transduction
D005227:Fatty Acids; D020738:Leptin; D008316:Malonyl Coenzyme A; D064429:Fatty Acid Synthases; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D005947:Glucose