INFLUENCE OF MALONYL-COA AND PALMITATE CONCENTRATION ON RATE OF PALMITATE OXIDATION IN RAT MUSCLE

5-Aminoimidazole-4-carboxamide l-beta-D-ribofuranoside (AICAR) is take n up by perfused skeletal muscle and phosphorylated to form 5-aminoimi dazole-4-carboxamide- 1-beta-D-ribofuraosyl-5'-monophosphate (analog o f 5'-AMP) with consequent activation of AMP-activated protein kinase, phosphorylation of acetyl-CoA carboxylase, decrease in malonyl-CoA, an d increase in fatty acid oxidation. This study was designed to determi ne the effect of increasing levels of palmitate on the rate of fatty a cid oxidation. Malonyl-CoA concentration was manipulated with AICAR at different palmitate concentrations. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine red cells, 200 mu U/ml insulin, 10 mM glucose, and different c oncentrations of palmitate (0.1-1.0 mM) without or with AICAR (2.0 mM) . Perfusion with medium containing AICAR was found to activate AMP-act ivated protein kinase in skeletal muscle, inactivate acetyl-CoA carbox ylase, and decrease malonyl-CoA at all concentrations of palmitate. Th e rate of palmitate oxidation increased as a function of palmitate con centration in both the presence and absence of AICAR but was always hi gher in the presence of AICAR. These results provide additional eviden ce that malonyl-CoA is an important regulator of the rate of fatty aci d oxidation at palmitate concentrations in the physiological range.