Role of malonyl-CoA in heart disease and the hypothalamic control of obesity

Cardiovascular Research

Volumn 73, Issue 2, 2007, Pages 278-287

  Folmes, Clifford D L ^a   Lopaschuk, Gary D ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

Acetyl CoA carboxylase; AMP activated protein kinase; Carnitine palmitoyltransferase 1; Fatty acid oxidation; Malonyl CoA; Malonyl CoA decarboxylase

Indexed keywords

CARNITINE PALMITOYLTRANSFERASE; CARNITINE PALMITOYLTRANSFERASE INHIBITOR; FATTY ACID; HEART ENZYME; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN; LONG CHAIN FATTY ACID COENZYME A LIGASE; MALONYL COENZYME A; MITOCHONDRIAL ENZYME; PYRUVIC ACID; STREPTOZOCIN;

BIOSYNTHESIS; ENERGY BALANCE; ENERGY EXPENDITURE; ENZYME ACTIVITY; ENZYME DEGRADATION; ENZYME INHIBITION; ENZYME MECHANISM; ENZYME PHOSPHORYLATION; ENZYME REGULATION; ENZYME SYNTHESIS; FATTY ACID OXIDATION; FATTY ACID TRANSPORT; FOOD INTAKE; HEART DISEASE; HEART MUSCLE METABOLISM; HUMAN; HYPOTHALAMUS; HYPOTHALAMUS FUNCTION; NONHUMAN; OBESITY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; WEIGHT GAIN;

ACETYL-COA CARBOXYLASE; ACYL COENZYME A; ANIMALS; APPETITE REGULATION; CARNITINE O-PALMITOYLTRANSFERASE; ENERGY METABOLISM; HEART DISEASES; HUMANS; HYPOTHALAMUS; MALONYL COENZYME A; MULTIENZYME COMPLEXES; OBESITY; PROTEIN-SERINE-THREONINE KINASES;

EID: 33845571750     PISSN: 00086363     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cardiores.2006.10.008     Document Type: Review

References (122)

1. Kopelman P.G., and Hitman G.A. Diabetes. Exploding type II. Lancet 352 Suppl 4 (1998) SIV5
2. Gwilt D.J., Petri M., Lewis P.W., Nattrass M., and Pentecost B.L. Myocardial infarct size and mortality in diabetic patients. Br Heart J 54 (1985) 466-772
3. Jaffe A.S., Spadaro J.J., Schechtman K., Roberts R., Geltman E.M., and Sobel B.E. Increased congestive heart failure after myocardial infarction of modest extent in patients with diabetes mellitus. Am Heart J 108 (1984) 31-37
4. Kannel W.B., and McGee D.L. Diabetes and cardiovascular risk factors: the Framingham study. Circulation 59 (1979) 8-13
5. Factor S.M., Minase T., and Sonnenblick E.H. Clinical and morphological features of human hypertensive-diabetic cardiomyopathy. Am Heart J 99 (1980) 446-458
6. Seneviratne B.I. Diabetic cardiomyopathy: the preclinical phase. Br Med J 1 (1977) 1444-1446
7. Poirier P., Bogaty P., Garneau C., Marois L., and Dumesnil J.G. Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy. Diabetes Care 24 (2001) 5-10
8. Redfield M.M., Jacobsen S.J., Burnett Jr. J.C., Mahoney D.W., Bailey K.R., and Rodeheffer R.J. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 289 (2003) 194-202
9. Hall J.L., Lopaschuk G.D., Barr A., Bringas J., Pizzurro R.D., and Stanley W.C. Increased cardiac fatty acid uptake with dobutamine infusion in swine is accompanied by a decrease in malonyl CoA levels. Cardiovasc Res 32 (1996) 879-885
10. Hall J.L., Stanley W.C., Lopaschuk G.D., Wisneski J.A., Pizzurro R.D., Hamilton C.D., et al. Impaired pyruvate oxidation but normal glucose uptake in diabetic pig heart during dobutamine-induced work. Am J Physiol Heart Circ Physiol 40 (1996) H2320-H2329
11. Kudo N., Barr A.J., Barr R.L., Desai S., and Lopaschuk G.D. High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5′-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J Biol Chem 270 (1995) 17513-17520
12. Thampy K.G. Formation of malonyl coenzyme-A in rat-heart - identification and purification of an isozyme of acetyl-coenzyme-A carboxylase from rat-heart. J Biol Chem 264 (1989) 17631-17634
13. Dyck J.R., Cheng J.F., Stanley W.C., Barr R., Chandler M.P., Brown S., et al. Malonyl coenzyme a decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation. Circ Res 94 (2004) 78-84
14. Kerner J., and Hoppel C.L. Radiochemical malonyl-CoA decarboxylase assay: activity and subcellular distribution in heart and skeletal muscle. Anal Biochem 306 (2002) 283-289
15. Kim Y.S., and Kolattukudy P.E. Purification and properties of malonyl-Coa decarboxylase from rat-liver mitochondria and its immunological comparison with enzymes from rat-brain, heart, and mammary-gland. Arch Biochem Biophys 190 (1978) 234-246
16. Saha A.K., Schwarsin A.J., Roduit R., Masse F., Kaushik V., Tornheim K., et al. Activation of malonyl-CoA decarboxylase in rat skeletal muscle by contraction and the AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside. J Biol Chem 275 (2000) 24279-24283
17. Reszko A.E., Kasumov T., Comte B., Pierce B.A., David F., Bederman I.R., et al. Assay of the concentration and 13C-isotopic enrichment of malonyl-coenzyme A by gas chromatography-mass spectrometry. Anal Biochem 298 (2001) 69-75
18. Kudo N., Gillespie J.G., Kung L., Witters L.A., Schulz R., Clanachan A.S., et al. Characterization of 5′AMP-activated protein kinase activity in the heart and its role in inhibiting acetyl-CoA carboxylase during reperfusion following ischemia. Biochim Biophys Acta 1301 (1996) 67-75
19. Dyck J.R., Kudo N., Barr A.J., Davies S.P., Hardie D.G., and Lopaschuk G.D. Phosphorylation control of cardiac acetyl-CoA carboxylase by cAMP-dependent protein kinase and 5′-AMP activated protein kinase. Eur J Biochem 262 (1999) 184-190
20. Munday M.R. Regulation of mammalian acetyl-CoA carboxylase. Biochem Soc Trans 30 (2002) 1059-1064
21. Joly E., Bendayan M., Roduit R., Saha A.K., Ruderman N.B., and Prentki M. Malonyl-CoA decarboxylase is present in the cytosolic, mitochondrial and peroxisomal compartments of rat hepatocytes. FEBS Lett 579 (2005) 6581-6586
22. Brown G.K., Scholem R.D., Bankier A., and Danks D.M. Malonyl coenzyme A decarboxylase deficiency. J Inherit Metab Dis 7 (1984) 21-26
23. Yano S., Sweetman L., Thorburn D.R., Mofidi S., and Williams J.C. A new case of malonyl coenzyme A decarboxylase deficiency presenting with cardiomyopathy. Eur J Pediatr 156 (1997) 382-383
24. Opie L.H. The heart: physiology, from cell to circulation (1998), Lippincott-Raven, Philadelphia, Pa
25. Neely J.R., and Morgan H.E. Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Annu Rev Physiol 36 (1974) 413-459
26. Stanley W.C., Recchia F.A., and Lopaschuk G.D. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85 (2005) 1093-1129
27. Mcgarry J.D., and Foster D.W. Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem 49 (1980) 395-420
28. Mcgarry J.D., Woeltje K.F., Kuwajima M., and Foster D.W. Regulation of ketogenesis and the renaissance of carnitine palmitoyltransferase. Diabetes Metab Rev 5 (1989) 271-284
29. King L.M., and Opie L.H. Glucose and glycogen utilisation in myocardial ischemia-changes in metabolism and consequences for the myocyte. Mol Cell Biochem 180 (1998) 3-26
30. Liu B., Clanachan A.S., Schulz R., and Lopaschuk G.D. Cardiac efficiency is improved after ischemia by altering both the source and fate of protons. Circ Res 79 (1996) 940-948
31. Liu B., el Alaoui-Talibi Z., Clanachan A.S., Schulz R., and Lopaschuk G.D. Uncoupling of contractile function from mitochondrial TCA cycle activity and MVO2 during reperfusion of ischemic hearts. Am J Physiol 270 (1996) H72-H80
32. Benzi R.H., and Lerch R. Dissociation between contractile function and oxidative metabolism in postischemic myocardium. Attenuation by ruthenium red administered during reperfusion. Circ Res 71 (1992) 567-576
33. Lopaschuk G.D., Spafford M.A., Davies N.J., and Wall S.R. Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia. Circ Res 66 (1990) 546-553
34. Saddik M., and Lopaschuk G.D. Myocardial triglyceride turnover and contribution to energy substrate utilization in isolated working rat hearts. J Biol Chem 266 (1991) 8162-8170
35. Oliver M.F., and Opie L.H. Effects of glucose and fatty acids on myocardial ischaemia and arrhythmias. Lancet 343 (1994) 155-158
36. Hardie D.G. AMP-activated protein kinase: a master switch in glucose and lipid metabolism. Rev Endocr Metab Disord 5 (2004) 119-125
37. Karmazyn M., and Moffat M.P. Na+/H+ exchange and regulation of intracellular Ca2+. Cardiovasc Res 27 (1993) 2079-2080
38. Solomon M.A., Jeffrey F.M., Storey C.J., Sherry A.D., and Malloy C.R. Substrate selection early after reperfusion of ischemic regions in the working rabbit heart. Magn Reson Med 35 (1996) 820-826
39. Tamm C., Benzi R., Papageorgiou I., Tardy I., and Lerch R. Substrate competition in postischemic myocardium. Effect of substrate availability during reperfusion on metabolic and contractile recovery in isolated rat hearts. Circ Res 75 (1994) 1103-1112
40. Sakamoto T., Aoki M., Imai Y., and Nemoto S. Carnitine affects fatty acid metabolism after cardioplegic arrest in neonatal rabbit hearts. Ann Thorac Surg 71 (2001) 648-653
41. Pietersen H.G., Langenberg C.J., Geskes G., Kester A., de L.S., Van d V., et al. Myocardial substrate uptake and oxidation during and after routine cardiac surgery. J Thorac Cardiovasc Surg 118 (1999) 71-80
42. Folmes C.D., Clanachan A.S., and Lopaschuk G.D. Fatty acid oxidation inhibitors in the management of chronic complications of atherosclerosis. Curr Atheroscler Rep 7 (2005) 63-70
43. Dyck J.R.B., Barr R., Jishage K., Watanabe M., Kawata Y., Nadzan A.M., et al. Hearts from malonyl CoA decarboxylase null mice are protected from ischemic damage. Circulation (2004) 322 [Abstract]
44. Goodale W.T., Olson R.E., and Hackel D.B. The effects of fasting and diabetes mellitus on myocardial metabolism in man. Am J Med 27 (1959) 212-220
45. Randle P.J., Garland P.B., Newsholme E.A., and Hales C.N. Glucose fatty-acid cycle - its role in insulin sensitivity and metabolic disturbances of diabetes mellitus. Lancet 1 (1963) 785-789
46. Wall S.R., and Lopaschuk G.D. Glucose oxidation rates in fatty acid-perfused isolated working hearts from diabetic rats. Biochim Biophys Acta 1006 (1989) 97-103
47. Sakamoto J., Barr R.L., Kavanagh K.M., and Lopaschuk G.D. Contribution of malonyl-CoA decarboxylase to the high fatty acid oxidation rates seen in the diabetic heart. Am J Physiol Heart Circ Physiol 278 (2000) 1196-1204
48. Lopaschuk G.D., and Tsang H. Metabolism of palmitate in isolated working hearts from spontaneously diabetic "BB" Wistar rats. Circ Res 61 (1987) 853-858
49. French T.J., Goode A.W., Holness M.J., MacLennan P.A., and Sugden M.C. The relationship between changes in lipid fuel availability and tissue fructose 2,6-bisphosphate concentrations and pyruvate dehydrogenase complex activities in the fed state. Biochem J 256 (1988) 935-939
50. Garland P.B., and Randle P.J. Regulation of glucose uptake by muscles. 10. Effects of alloxan-diabetes, starvation, hypophysectomy and adrenalectomy, and of fatty acids, ketone bodies and pyruvate, on the glycerol output and concentrations of free fatty acids, long-chain fatty acyl-coenzyme A, glycerol phosphate and citrate-cycle intermediates in rat heart and diaphragm muscles. Biochem J 93 (1964) 678-687
51. Aasum E., Belke D.D., Severson D.L., Riemersma R.A., Cooper M., Andreassen M., et al. Cardiac function and metabolism in Type 2 diabetic mice after treatment with BM 17.0744, a novel PPAR-alpha activator. Am J Physiol Heart Circ Physiol 283 (2002) 949-957
52. Ramanathan T., Shirota K., Morita S., Nishimura T., Huang Y., Zheng X., et al. Left ventricular oxygen utilization efficiency is impaired in chronic streptozotocin-diabetic sheep. Cardiovasc Res 55 (2002) 749-756
53. Gamble J., and Lopaschuk G.D. Glycolysis and glucose oxidation during reperfusion of ischemic hearts from diabetic rats. Biochim Biophys Acta 1225 (1994) 191-199
54. Gamble J., and Lopaschuk G.D. Insulin inhibition of 5′ adenosine monophosphate-activated protein kinase in the heart results in activation of acetyl coenzyme A carboxylase and inhibition of fatty acid oxidation. Metabolism 46 (1997) 1270-1274
55. Zhou Y.T., Grayburn P., Karim A., Shimabukuro M., Higa M., Baetens D., et al. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A 97 (2000) 1784-1789
56. Unger R.H. Lipotoxic diseases. Annu Rev Med 53 (2002) 319-336
57. Unger R.H. Hyperleptinemia: protecting the heart from lipid overload. Hypertension 45 (2005) 1031-1034
58. Abu-Elheiga L., Matzuk M.M., Abo-Hashema K.A., and Wakil S.J. Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 291 (2001) 2613-2616
59. Taegtmeyer H., McNulty P., and Young M.E. Adaptation and maladaptation of the heart in diabetes: part I general concepts. Circulation 105 (2002) 1727-1733
60. Unger R.H., Zhou Y.T., and Orci L. Regulation of fatty acid homeostasis in cells: novel role of leptin. Proc Natl Acad Sci U S A 96 (1999) 2327-2332
61. Chiu H.C., Kovacs A., Ford D.A., Hsu F.F., Garcia R., Herrero P., et al. A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest 107 (2001) 813-822
62. Chen H.C., and Farese Jr. R.V. Fatty acids, triglycerides, and glucose metabolism: recent insights from knockout mice. Curr Opin Clin Nutr Metab Care 5 (2002) 359-363
63. Lee Y., Yu X., Gonzales F., Mangelsdorf D.J., Wang M.Y., Richardson C., et al. PPAR alpha is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue. Proc Natl Acad Sci U S A 99 (2002) 11848-11853
64. Atkinson L.L., Fischer M.A., and Lopaschuk G.D. Leptin activates cardiac fatty acid oxidation independent of changes in the AMP-activated protein kinase-acetyl-CoA carboxylase-malonyl-CoA axis. J Biol Chem 277 (2002) 29424-29430
65. Atkinson L.L., Kozak R., Kelly S.E., Onay Besikci A., Russell J.C., and Lopaschuk G.D. Potential mechanisms and consequences of cardiac triacylglycerol accumulation in insulin-resistant rats. Am J Physiol Endocrinol Metab 284 (2003) 923-930
66. Young M.E., McNulty P., and Taegtmeyer H. Adaptation and maladaptation of the heart in diabetes: part II - potential mechanisms. Circulation 105 (2002) 1861-1870
67. Young M.E., Guthrie P.H., Razeghi P., Leighton B., Abbasi S., Patil S., et al. Impaired long-chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart. Diabetes 51 (2002) 2587-2595
68. Oakes N.D., Thalen P., Aasum E., Edgley A., Larsen T., Furler S.M., et al. Cardiac metabolism in mice: tracer method developments and in vivo application revealing profound metabolic inflexibility in diabetes. AJP- Endocrinol. Metab. 290 (2006) E870-E881
69. Turpeinen A.K., Kuikka J.T., Vanninen E., and Uusitupa M.I. Abnormal myocardial kinetics of 123I-heptadecanoic acid in subjects with impaired glucose tolerance. Diabetologia 40 (1997) 541-549
70. Mazumder P.K., O'Neill B.T., Roberts M.W., Buchanan J., Yun U.J., Cooksey R.C., et al. Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes 53 (2004) 2366-2374
71. Carroll R., Carley A.N., Dyck J.R., and Severson D.L. Metabolic effects of insulin on cardiomyocytes from control and diabetic db/db mouse hearts. Am J Physiol Endocrinol Metab 288 (2005) 900-906
72. Belke D.D., Larsen T.S., Gibbs E.M., and Severson D.L. Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice. Am J Physiol Endocrinol Metab 279 (2000) 1104-1113
73. Lopaschuk G.D., and Russell J.C. Myocardial function and energy substrate metabolism in the insulin-resistant JCR:LA corpulent rat. J Appl Physiol 71 (1991) 1302-1308
74. Peterson L.R., Herrero P., Schechtman K.B., Racette S.B., Waggoner A.D., Kisrieva-Ware Z., et al. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 109 (2004) 2191-2196
75. Hearse D.J., Stewart D.A., and Chain E.B. Diabetes and the survival and recovery of the anoxic myocardium. J Mol Cell Cardiol 7 (1975) 397-415
76. Feuvray D., Idell-Wenger J.A., and Neely J.R. Effects of ischemia on rat myocardial function and metabolism in diabetes. Circ Res 44 (1979) 322-329
77. Hekimian G., and Feuvray D. Reduction of ischemia-induced acyl carnitine accumulation by TDGA and its influence on lactate dehydrogenase release in diabetic rat hearts. Diabetes 35 (1986) 906-910
78. Tani M., and Neely J.R. Hearts from diabetic rats are more resistant to in vitro ischemia: possible role of altered Ca2+ metabolism. Circ Res 62 (1988) 931-940
79. Lopaschuk G.D., Saddik M., Barr R., Huang L., Barker C.C., and Muzyka R.A. Effects of high levels of fatty acids on functional recovery of ischemic hearts from diabetic rats. Am J Physiol 263 (1992) E1046-E1053
80. Paulson D.J., Kopp S.J., Peace D.G., and Tow J.P. Improved postischemic recovery of cardiac pump function in exercised trained diabetic rats. J Appl Physiol 65 (1988) 187-193
81. Pieper G.M., and Gross G.J. Diabetes alters postischemic response to a prostacyclin mimetic. Am J Physiol 256 (1989) H1353-H1360
82. Lopaschuk G.D. Metabolic abnormalities in the diabetic heart. Heart Fail Rev 7 (2002) 149-159
83. Feuvray D., and Lopaschuk G.D. Controversies on the sensitivity of the diabetic heart to ischemic injury: the sensitivity of the diabetic heart to ischemic injury is decreased. Cardiovasc Res 34 (1997) 113-120
84. Schwartz M.W., Woods S.C., Porte D., Seeley R.J., and Baskin D.G. Central nervous system control of food intake. Nature 404 (2000) 661-671
85. Zigman J.M., and Elmquist J.K. Minireview: from anorexia to obesity-the yin and yang of body weight control. Endocrinology 144 (2003) 3749-3756
86. Niswender K.D., Baskin D.G., and Schwartz M.W. Insulin and its evolving partnership with leptin in the hypothalamic control of energy homeostasis. Trends Endocrinol Metab 15 (2004) 362-369
87. Morgan K., Obici S., and Rossetti L. Hypothalamic responses to long-chain fatty acids are nutritionally regulated. J Biol Chem 279 (2004) 31139-31148
88. Langhans W., Damaske U., and Scharrer E. Different metabolites might reduce food intake by the mitochondrial generation of reducing equivalents. Appetite 6 (1985) 143-152
89. Friedman J.M., and Halaas J.L. Leptin and the regulation of body weight in mammals. Nature 395 (1998) 763-770
90. Lachey J.L., D'Alessio D.A., Rinaman L., Elmquist J.K., Drucker D.J., and Seeley R.J. The role of central GLP-1 in mediating the effects of visceral illness: differential effects in rats and mice. Endocrinology 46 (2004) 458-462
91. Minokoshi Y., Alquier T., Furukawa N., Kim Y.B., Lee A., Xue B., et al. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428 (2004) 569-574
92. Kubota N., Terauchi Y., Tobe K., Yano W., Suzuki R., Ueki K., et al. Insulin receptor substrate 2 plays a crucial role in beta cells and the hypothalamus. J Clin Invest 114 (2004) 917-927
93. Obici S., Feng Z., Karkanias G., Baskin D.G., and Rossetti L. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat Neurosci 5 (2002) 566-572
94. Kim M.S., Park J.Y., Namkoong C., Jang P.G., Ryu J.W., Song H.S., et al. Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nat Med 10 (2004) 727-733
95. Qi Y., Takahashi N., Hileman S.M., Patel H.R., Berg A.H., Pajvani U.B., et al. Adiponectin acts in the brain to decrease body weight. Nat Med 10 (2004) 524-529
96. Kim E.K., Miller I., Aja S., Landree L.E., Pinn M., McFadden J., et al. C75, a fatty acid synthase inhibitor, reduces food intake via hypothalamic AMP-activated protein kinase. J Biol Chem 279 (2004) 19970-19976
97. Andersson U., Filipsson K., Abbott C.R., Woods A., Smith K., Bloom S.R., et al. AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem 279 (2004) 12005-12008
98. McCrimmon R.J., Fan X., Ding Y., Zhu W., Jacob R.J., and Sherwin R.S. Potential role for AMP-activated protein kinase in hypoglycemia sensing in the ventromedial hypothalamus. Diabetes 53 (2004) 1953-1958
99. Kola B., Hubina E., Tucci S.A., Kirkham T.C., Garcia E.A., Mitchell S.E., et al. Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase. J Biol Chem 280 (2005) 25196-25201
100. Schwartz M.W. Neuronal pathways regulating food intake and body adiposity. Ann Endocrinol (Paris) 63 (2002) 117-120
101. Lee K., Li B., Xi X., Suh Y., and Martin R.J. The role of neuronal energy status in the regulation of AMP-activated protein kinase, orexigenic neuropeptides expression and feeding behavior. Endocrinology 146 (2005) 3-10
102. Niswender K.D., Morrison C.D., Clegg D.J., Olson R., Baskin D.G., Myers Jr. M.G., et al. Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. Diabetes 52 (2003) 227-231
103. Benoit S.C., Air E.L., Coolen L.M., Strauss R., Jackman A., Clegg D.J., et al. The catabolic action of insulin in the brain is mediated by melanocortins. J Neurosci 22 (2002) 9048-9052
104. Makinde A.O., Gamble J., and Lopaschuk G.D. Upregulation of 5′-AMP-activated protein kinase is responsible for the increase in myocardial fatty acid oxidation rates following birth in the newborn rabbit. Circ Res 80 (1997) 482-489
105. Folmes C.D., Clanachan A.S., and Lopaschuk G.D. Fatty acids attenuate insulin regulation of 5′-AMP-activated protein kinase and insulin cardioprotection after ischemia. Circ Res 99 (2006) 61-68
106. Clark H., Carling D., and Saggerson D. Covalent activation of heart AMP-activated protein kinase in response to physiological concentrations of long-chain fatty acids. Eur J Biochem 271 (2004) 2215-2224
107. Hue L., Beauloye C., Marsin A.S., Bertrand L., Horman S., and Rider M.H. Insulin and ischemia stimulate glycolysis by acting on the same targets through different and opposing signaling pathways. J Mol Cell Cardiol 34 (2002) 1091-1097
108. Witters L.A., and Kemp B.E. Insulin activation of acetyl-CoA carboxylase accompanied by inhibition of the 5′-AMP-activated protein kinase. J Biol Chem 267 (1992) 2864-2867
109. Horman S., Vertommen D., Heath R., Neumann D., Mouton V., Woods A., et al. Insulin antagonizes ischemia-induced THR172 phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of SER485/491. J Biol Chem 281 (2006) 5335-5340
110. Hu Z., Cha S.H., Chohnan S., and Lane M.D. Hypothalamic malonyl-CoA as a mediator of feeding behavior. Proc Natl Acad Sci U S A 100 (2003) 12624-12629
111. Kim E.K., Miller I., Landree L.E., Borisy-Rudin F.F., Brown P., Tihan T., et al. Expression of FAS within hypothalamic neurons: a model for decreased food intake after C75 treatment. Am J Physiol Endocrinol Metab 283 (2002) 867-879
112. Landree L.E., Hanlon A.L., Strong D.W., Rumbaugh G., Miller I.M., Thupari J.N., et al. C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism. J Biol Chem 279 (2004) 3817-3827
113. Tu Y., Thupari J.N., Kim E.K., Pinn M.L., Moran T.H., Ronnett G.V., et al. C75 alters central and peripheral gene expression to reduce food intake and increase energy expenditure. Endocrinology 146 (2005) 486-493
114. Miller I., Ronnett G.V., Moran T.H., and Aja S. Anorexigenic C75 alters c-Fos in mouse hypothalamic and hindbrain subnuclei. Neuroreport 15 (2004) 925-929
115. Cha S.H., Hu Z., and Lane M.D. Long-term effects of a fatty acid synthase inhibitor on obese mice: food intake, hypothalamic neuropeptides, and UCP3. Biochem Biophys Res Commun 317 (2004) 301-308
116. Takahashi K.A., Smart J.L., Liu H., and Cone R.D. The anorexigenic fatty acid synthase inhibitor, C75, is a nonspecific neuronal activator. Endocrinology 145 (2004) 184-193
117. Lam T.K., Gutierrez-Juarez R., Pocai A., and Rossetti L. Regulation of blood glucose by hypothalamic pyruvate metabolism. Science 309 (2005) 943-947
118. Lam T.K., Schwartz G.J., and Rossetti L. Hypothalamic sensing of fatty acids. Nat Neurosci 8 (2005) 579-584
119. Lam T.K., Pocai A., Gutierrez-Juarez R., Obici S., Bryan J., Aguilar-Bryan L., et al. Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis. Nat Med 11 (2005) 320-327
120. He W., Lam T.K., Obici S., and Rossetti L. Molecular disruption of hypothalamic nutrient sensing induces obesity. Nat Neurosci 9 (2006) 227-233
121. Obici S., and Rossetti L. Minireview: nutrient sensing and the regulation of insulin action and energy balance. Endocrinology 144 (2003) 5172-5178
122. Cha S.H., Hu Z., Chohnan S., and Lane M.D. Inhibition of hypothalamic fatty acid synthase triggers rapid activation of fatty acid oxidation in skeletal muscle. Proc Natl Acad Sci U S A 102 (2005) 14557-14562