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1 Department of Biological Sciences, Rutgers University, New Brunswick, New Jersey 98903; 2 Zoology Department, Brigham Young University, Provo, Utah 84602; and 3 Department of Biochemistry, The University, Dundee DD1 4HN, Scotland, United Kingdom
5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has previously been reported to be taken up into cells and phosphorylated to form ZMP, an analog of 5'-AMP. This study was designed to determine whether AICAR can activate AMP-activated protein kinase (AMPK) in skeletal muscle with consequent phosphorylation of acetyl-CoA carboxylase (ACC), decrease in malonyl-CoA, and increase in fatty acid oxidation. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine red blood cells, 200 µU/ml insulin, and 10 mM glucose with or without AICAR (0.5-2.0 mM). Perfusion with medium containing AICAR was found to activate AMPK in skeletal muscle, inactivate ACC, and decrease malonyl-CoA. Hindlimbs perfused with 2 mM AICAR for 45 min exhibited a 2.8-fold increase in fatty acid oxidation and a significant increase in glucose uptake. No difference was observed in oxygen uptake in AICAR vs. control hindlimb. These results provide evidence that decreases in muscle content of malonyl-CoA can increase the rate of fatty acid oxidation.
acetyl-CoA carboxylase; malonyl-CoA; palmitate oxidation; 5-aminoimidazole-4-carboxamide riboside; ZMP
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E. B. Taylor, D. Hurst, L. J. Greenwood, J. D. Lamb, T. D. Cline, S. N. Sudweeks, and W. W. Winder Endurance training increases LKB1 and MO25 protein but not AMP-activated protein kinase kinase activity in skeletal muscle Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1082 - E1089. [Abstract] [Full Text] [PDF]
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H. Yu, N. Fujii, M. F. Hirshman, J. M. Pomerleau, and L. J. Goodyear Cloning and characterization of mouse 5'-AMP-activated protein kinase {gamma}3 subunit Am J Physiol Cell Physiol, February 1, 2004; 286(2): C283 - C292. [Abstract] [Full Text]
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M. J. Christopher, Z.-P. Chen, C. Rantzau, B. E. Kemp, and F. P. Alford Skeletal muscle basal AMP-activated protein kinase activity is chronically elevated in alloxan-diabetic dogs: impact of exercise J Appl Physiol, October 1, 2003; 95(4): 1523 - 1530. [Abstract] [Full Text] [PDF]
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M. Suwa, H. Nakano, and S. Kumagai Effects of chronic AICAR treatment on fiber composition, enzyme activity, UCP3, and PGC-1 in rat muscles J Appl Physiol, September 1, 2003; 95(3): 960 - 968. [Abstract] [Full Text] [PDF]
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D. L. Coven, X. Hu, L. Cong, R. Bergeron, G. I. Shulman, D. G. Hardie, and L. H. Young Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E629 - E636. [Abstract] [Full Text] [PDF]
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G. R. Steinberg, J. W. E. Rush, and D. J. Dyck AMPK expression and phosphorylation are increased in rodent muscle after chronic leptin treatment Am J Physiol Endocrinol Metab, March 1, 2003; 284(3): E648 - E654. [Abstract] [Full Text] [PDF]
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S. H. Park, S. R. Paulsen, S. R. Gammon, K. J. Mustard, D. G. Hardie, and W. W. Winder Effects of thyroid state on AMP-activated protein kinase and acetyl-CoA carboxylase expression in muscle J Appl Physiol, December 1, 2002; 93(6): 2081 - 2088. [Abstract] [Full Text] [PDF]
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J. Stoppani, A. L. Hildebrandt, K. Sakamoto, D. Cameron-Smith, L. J. Goodyear, and P. D. Neufer AMP-activated protein kinase activates transcription of the UCP3 and HKII genes in rat skeletal muscle Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1239 - E1248. [Abstract] [Full Text] [PDF]
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L. L. Tortorella and P. F. Pilch C2C12 myocytes lack an insulin-responsive vesicular compartment despite dexamethasone-induced GLUT4 expression Am J Physiol Endocrinol Metab, September 1, 2002; 283(3): E514 - E524. [Abstract] [Full Text] [PDF]
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