This Article Full Text Full Text (PDF) All Versions of this Article: 144/12/5166    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ruderman, N. B. Articles by Kraegen, E. W. Search for Related Content PubMed PubMed Citation Articles by Ruderman, N. B. Articles by Kraegen, E. W.

Minireview: Malonyl CoA, AMP-Activated Protein Kinase, and Adiposity

Departments of Medicine, Physiology, and Biophysics (N.B.R., A.K.S.), Boston University School of Medicine and Diabetes Unit, Section of Endocrinology, Boston Medical Center, Boston, Massachusetts 02118; and Garvan Institute (E.W.K.), Sydney, New South Wales 2010, Australia

Address all correspondence and requests for reprints to: Neil Ruderman, M.D., D.Phil., Diabetes Unit, Boston Medical Center, 650 Albany Street, X825, Boston, Massachusetts 02118. E-mail: nruderman{at}medicine.bu.edu.

An increasing body of evidence has linked AMP-activated protein kinase (AMPK) and malonyl coenzyme A (CoA) to the regulation of energy balance. Thus, factors that activate AMPK and decrease the concentration of malonyl CoA in peripheral tissues, such as exercise, decrease triglyceride accumulation in the adipocyte and other cells. The data reviewed here suggest that this is related to the fact that these factors concurrently increase fatty acid oxidation, decrease the esterification of fatty acids to form glycerolipids, and, by mechanisms still unknown, increase energy expenditure. Malonyl CoA contributes to these events because it is an allosteric inhibitor of carnitine palmitoyltransferase, the enzyme that controls the transfer of long-chain fatty acyl CoA from the cytosol to the mitochondria, where they are oxidized. AMPK activation in turn increases fatty acid oxidation (by effects on enzymes that govern malonyl CoA synthesis and possibly its degradation) and inhibits triglyceride synthesis. It also increases the expression of uncoupling proteins and the transcriptional regulator peroxisome proliferator-activated receptor coactivator-1 (PGC1), which could possibly increase energy expenditure. Recent studies suggest that the ability of leptin, adiponectin, 5'-aminoimidazole 4-carboxamide riboside (AICAR), adrenergic agonists, and metformin to diminish adiposity may be mediated, at least in part, by AMPK activation in peripheral tissues. In addition, preliminary studies suggest that malonyl CoA and AMPK take part in fuel-sensing and signaling mechanisms in the hypothalamus that could regulate food intake and energy expenditure.

This article has been cited by other articles:

				U. Riek, R. Scholz, P. Konarev, A. Rufer, M. Suter, A. Nazabal, P. Ringler, M. Chami, S. A. Muller, D. Neumann, et al. Structural Properties of AMP-activated Protein Kinase: DIMERIZATION, MOLECULAR SHAPE, AND CHANGES UPON LIGAND BINDING J. Biol. Chem., June 27, 2008; 283(26): 18331 - 18343. [Abstract] [Full Text] [PDF]

				R. Roberts, A. S Bickerton, B. A Fielding, E. E Blaak, A. J Wagenmakers, M. F-F Chong, M. Gilbert, F. Karpe, and K. N Frayn Reduced oxidation of dietary fat after a short term high-carbohydrate diet Am. J. Clinical Nutrition, April 1, 2008; 87(4): 824 - 831. [Abstract] [Full Text] [PDF]

				P. G. Cammisotto, I. Londono, D. Gingras, and M. Bendayan Control of glycogen synthase through ADIPOR1-AMPK pathway in renal distal tubules of normal and diabetic rats Am J Physiol Renal Physiol, April 1, 2008; 294(4): F881 - F889. [Abstract] [Full Text] [PDF]

				M. E. Osler and J. R. Zierath Minireview: Adenosine 5'-Monophosphate-Activated Protein Kinase Regulation of Fatty Acid Oxidation in Skeletal Muscle Endocrinology, March 1, 2008; 149(3): 935 - 941. [Abstract] [Full Text] [PDF]

				K. Shinmura, K. Tamaki, K. Saito, Y. Nakano, T. Tobe, and R. Bolli Cardioprotective Effects of Short-Term Caloric Restriction Are Mediated by Adiponectin via Activation of AMP-Activated Protein Kinase Circulation, December 11, 2007; 116(24): 2809 - 2817. [Abstract] [Full Text] [PDF]

				Pieter de Lange, M. Moreno, E. Silvestri, A. Lombardi, F. Goglia, and A. Lanni Fuel economy in food-deprived skeletal muscle: signaling pathways and regulatory mechanisms FASEB J, November 1, 2007; 21(13): 3431 - 3441. [Abstract] [Full Text] [PDF]

				S. Paglialunga, P. Schrauwen, C. Roy, E. Moonen-Kornips, H. Lu, M. K C Hesselink, Y. Deshaies, D. Richard, and K. Cianflone Reduced adipose tissue triglyceride synthesis and increased muscle fatty acid oxidation in C5L2 knockout mice J. Endocrinol., August 1, 2007; 194(2): 293 - 304. [Abstract] [Full Text] [PDF]

				E. J. Kim, S.-N. Jung, K. H. Son, S. R. Kim, T. Y. Ha, M. G. Park, I. G. Jo, J. G. Park, W. Choe, S.-S. Kim, et al. Antidiabetes and Antiobesity Effect of Cryptotanshinone via Activation of AMP-Activated Protein Kinase Mol. Pharmacol., July 1, 2007; 72(1): 62 - 72. [Abstract] [Full Text] [PDF]

				I. Bogacka, T. W. Gettys, L. de Jonge, T. Nguyen, J. M. Smith, H. Xie, F. Greenway, and S. R. Smith The Effect of {beta}-Adrenergic and Peroxisome Proliferator-Activated Receptor-{gamma} Stimulation on Target Genes Related to Lipid Metabolism in Human Subcutaneous Adipose Tissue Diabetes Care, May 1, 2007; 30(5): 1179 - 1186. [Abstract] [Full Text] [PDF]

				W. Zhou, W. F. Han, L. E. Landree, J. N. Thupari, M. L. Pinn, T. Bililign, E. K. Kim, A. Vadlamudi, S. M. Medghalchi, R. El Meskini, et al. Fatty Acid Synthase Inhibition Activates AMP-Activated Protein Kinase in SKOV3 Human Ovarian Cancer Cells Cancer Res., April 1, 2007; 67(7): 2964 - 2971. [Abstract] [Full Text] [PDF]

				C. A. Stuart, M. E.A. Howell, and D. Yin Overexpression of GLUT5 in Diabetic Muscle Is Reversed by Pioglitazone Diabetes Care, April 1, 2007; 30(4): 925 - 931. [Abstract] [Full Text] [PDF]

				A Corbould Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women J. Endocrinol., March 1, 2007; 192(3): 585 - 594. [Abstract] [Full Text] [PDF]

				M. P. Gaidhu, S. Fediuc, and R. B. Ceddia 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced AMP-activated Protein Kinase Phosphorylation Inhibits Basal and Insulin-stimulated Glucose Uptake, Lipid Synthesis, and Fatty Acid Oxidation in Isolated Rat Adipocytes J. Biol. Chem., September 8, 2006; 281(36): 25956 - 25964. [Abstract] [Full Text] [PDF]

				H. Yu, M. F. Hirshman, N. Fujii, J. M. Pomerleau, L. E. Peter, and L. J. Goodyear Muscle-specific overexpression of wild type and R225Q mutant AMP-activated protein kinase {gamma}3-subunit differentially regulates glycogen accumulation Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E557 - E565. [Abstract] [Full Text] [PDF]

				D. Qi, D. An, G. Kewalramani, Y. Qi, T. Pulinilkunnil, A. Abrahani, U. Al-Atar, S. Ghosh, R. B. Wambolt, M. F. Allard, et al. Altered cardiac fatty acid composition and utilization following dexamethasone-induced insulin resistance Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E420 - E427. [Abstract] [Full Text] [PDF]

				S. Ramamurthy and G. V. Ronnett Developing a head for energy sensing: AMP-activated protein kinase as a multifunctional metabolic sensor in the brain J. Physiol., July 1, 2006; 574(1): 85 - 93. [Abstract] [Full Text] [PDF]

				L. Qi, J. E. Heredia, J. Y. Altarejos, R. Screaton, N. Goebel, S. Niessen, I. X. MacLeod, C. W. Liew, R. N. Kulkarni, J. Bain, et al. TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism. Science, June 23, 2006; 312(5781): 1763 - 1766. [Abstract] [Full Text] [PDF]

				J.-M. Brusq, N. Ancellin, P. Grondin, R. Guillard, S. Martin, Y. Saintillan, and M. Issandou Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine J. Lipid Res., June 1, 2006; 47(6): 1281 - 1288. [Abstract] [Full Text] [PDF]

				E. Prodi and S. Obici Minireview: The Brain as a Molecular Target for Diabetic Therapy Endocrinology, June 1, 2006; 147(6): 2664 - 2669. [Abstract] [Full Text] [PDF]

				M. Lopez, C. J. Lelliott, S. Tovar, W. Kimber, R. Gallego, S. Virtue, M. Blount, M. J. Vazquez, N. Finer, T. J. Powles, et al. Tamoxifen-Induced Anorexia Is Associated With Fatty Acid Synthase Inhibition in the Ventromedial Nucleus of the Hypothalamus and Accumulation of Malonyl-CoA. Diabetes, May 1, 2006; 55(5): 1327 - 1336. [Abstract] [Full Text] [PDF]

				E. B. Taylor, J. D. Lamb, R. W. Hurst, D. G. Chesser, W. J. Ellingson, L. J. Greenwood, B. B. Porter, S. T. Herway, and W. W. Winder Endurance training increases skeletal muscle LKB1 and PGC-1{alpha} protein abundance: effects of time and intensity Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E960 - E968. [Abstract] [Full Text] [PDF]

				H. Bruunsgaard Physical activity and modulation of systemic low-level inflammation J. Leukoc. Biol., October 1, 2005; 78(4): 819 - 835. [Abstract] [Full Text] [PDF]

				J. Park, H. K. Rho, K. H. Kim, S. S. Choe, Y. S. Lee, and J. B. Kim Overexpression of Glucose-6-Phosphate Dehydrogenase Is Associated with Lipid Dysregulation and Insulin Resistance in Obesity Mol. Cell. Biol., June 15, 2005; 25(12): 5146 - 5157. [Abstract] [Full Text] [PDF]

				D. An, G. Kewalramani, D. Qi, T. Pulinilkunnil, S. Ghosh, A. Abrahani, R. Wambolt, M. Allard, S. M. Innis, and B. Rodrigues {beta}-Agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1120 - E1127. [Abstract] [Full Text] [PDF]

				M. A. Maxwell, M. E. Cleasby, A. Harding, A. Stark, G. J. Cooney, and G. E. O. Muscat Nur77 Regulates Lipolysis in Skeletal Muscle Cells: EVIDENCE FOR CROSS-TALK BETWEEN THE {beta}-ADRENERGIC AND AN ORPHAN NUCLEAR HORMONE RECEPTOR PATHWAY J. Biol. Chem., April 1, 2005; 280(13): 12573 - 12584. [Abstract] [Full Text] [PDF]

				M.-y. Wang and R. H. Unger Role of PP2C in cardiac lipid accumulation in obese rodents and its prevention by troglitazone Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E216 - E221. [Abstract] [Full Text] [PDF]

				C. Bouche, S. Serdy, C. R. Kahn, and A. B. Goldfine The Cellular Fate of Glucose and Its Relevance in Type 2 Diabetes Endocr. Rev., October 1, 2004; 25(5): 807 - 830. [Abstract] [Full Text] [PDF]

				J. A. Villena, B. Viollet, F. Andreelli, A. Kahn, S. Vaulont, and H. S. Sul Induced Adiposity and Adipocyte Hypertrophy in Mice Lacking the AMP-Activated Protein Kinase-{alpha}2 Subunit Diabetes, September 1, 2004; 53(9): 2242 - 2249. [Abstract] [Full Text] [PDF]

				E.-K. Kim, I. Miller, S. Aja, L. E. Landree, M. Pinn, J. McFadden, F. P. Kuhajda, T. H. Moran, and G. V. Ronnett C75, a Fatty Acid Synthase Inhibitor, Reduces Food Intake via Hypothalamic AMP-activated Protein Kinase J. Biol. Chem., May 7, 2004; 279(19): 19970 - 19976. [Abstract] [Full Text] [PDF]

				U. Andersson, K. Filipsson, C. R. Abbott, A. Woods, K. Smith, S. R. Bloom, D. Carling, and C. J. Small AMP-activated Protein Kinase Plays a Role in the Control of Food Intake J. Biol. Chem., March 26, 2004; 279(13): 12005 - 12008. [Abstract] [Full Text] [PDF]

				S. Obici and L. Rossetti Minireview: Nutrient Sensing and the Regulation of Insulin Action and Energy Balance Endocrinology, December 1, 2003; 144(12): 5172 - 5178. [Abstract] [Full Text] [PDF]