High carbohydrate availability increases LCFA uptake and decreases LCFA oxidation in perfused muscle

To determine whether changes in long-chain fatty acid (LCFA) oxidative metabolism induced by elevated intracellular carbohydrate availability are due to changes in LCFA uptake or in mitochondrial transport capacity, rat hindquarters were perfused with 500 muM palmitate and [1-C-14] palmitate or [1-C-14] octanoate as well as with either low (LG) or high (HG) carbohydrate availability. Glucose uptake was higher in the HG vs. LG group (23.6 +/- 1.5 vs 4.7 +/- 0.9 mu mol.g(-1).h(-1), P< 0.05). Palmitate delivery was not significantly different between groups and averaged 97.1 +/- 4.6 nmol.min(-1).g(-1) (P> 0.05). Fractional and total palmitate uptake values were 60% higher (P< 0.05) in the HG (0.125 +/- 0.012 and 7.4 +/- 1.2 nmol.min(-1).g(-1)) vs. LG (0.079 +/- 0.009 and 11.8 +/- 1.5 nmol.min(-1).g(-1)) group. Values of percent and total palmitate oxidized were significantly lower (P<0.05) in the HG (9.1 +/- 1.1% and 1.31 +/- 0.16 nmol.min(-1).g(-1)) vs. LG (23.4 +/- 5.2% and 0.76 +/- 0.08 nmol.min(-1).g(-1)) group. Conversely, values of fractional uptake and percent oxidation of octanoate were not significantly different between groups (P> 0.05). Malonyl-CoA levels were inversely correlated with LCFA oxidation (P< 0.05). These results demonstrate that high carbohydrate availability in muscle is associated with a decrease in LCFA oxidation that is not due to a parallel decrease in LCFA uptake; rather, the decrease in LCFA oxidation could be due to malonyl-CoA inhibition of mitochondrial LCFA transport.