The brain plays an important role in the regulation of energy balance in higher animals. Global energy balance is monitored by sets of neurons in the hypothalamus that respond to peripheral hormonal and afferent neural signals that sense the energy status. Malonyl-CoA, an intermediate in the biosynthesis of fatty acids, appears to function in this hypothalamic energy-sensing system. The steady-state level of malonyl-CoA is determined by its rate of synthesis catalysed by ACC (acetyl-CoA carboxylase) relative to its rate of turnover catalysed by FAS (fatty acid synthase). Changes in the level of malonyl-CoA in the hypothalamus alter the expression/secretion of key hypothalamic orexigenic and anorexigenic neuropeptides that regulate the feeding behaviour and energy expenditure. Inhibitors of FAS, administered i.c.v. (intracerebroventricularly) to lean or obese mice, cause a rapid rise in hypothalamic malonyl-CoA level, suppression of food intake, increased fatty acid oxidation in skeletal muscle and profound weight loss. Stereotactic delivery of a viral MCD (malonyl-CoA decarboxylase) expression vector into the ventral hypothalamus lowers malonyl-CoA levels and reverses the anorectic effect of the FAS inhibitors. Fasting decreases, whereas refeeding increases, hypothalamic malonyl-CoA and alters subsequent feeding behaviour accordingly. The level of malonyl-CoA in the hypothalamus appears to be under the control of 5′-AMP kinase, which phosphorylates and thereby inactivates ACC under conditions of energy surplus. Thus malonyl-CoA appears to link the energy-responsive fatty acid synthesis in the hypothalamus to feeding behaviour and peripheral energy expenditure.
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October 2005
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Conference Article|
October 26 2005
Role of malonyl-CoA in the hypothalamic control of food intake and energy expenditure
M.D. Lane;
M.D. Lane
1
1Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, U.S.A.
1To whom correspondence should be addressed (email dlane@jhmi.edu).
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Z. Hu;
Z. Hu
1Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, U.S.A.
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S.-H. Cha;
S.-H. Cha
1Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, U.S.A.
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Y. Dai;
Y. Dai
1Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, U.S.A.
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M. Wolfgang;
M. Wolfgang
1Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, U.S.A.
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A. Sidhaye
A. Sidhaye
1Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, U.S.A.
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Biochem Soc Trans (2005) 33 (5): 1063–1067.
Article history
Received:
July 05 2005
Citation
M.D. Lane, Z. Hu, S.-H. Cha, Y. Dai, M. Wolfgang, A. Sidhaye; Role of malonyl-CoA in the hypothalamic control of food intake and energy expenditure. Biochem Soc Trans 26 October 2005; 33 (5): 1063–1067. doi: https://doi.org/10.1042/BST0331063
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