Effects of high fat provision on muscle PDH activation and malonyl-CoA content in moderate exercise

This study examined the effects of elevated free fatty acid (FFA) provision on the regulation of pyruvate dehydrogenase (PDH) activity and malonyl-CoA (M-CoA) content in human skeletal muscle during moderate-intensity exercis e. Seven men rested for 30 min and cycled for 10 min at 40% and 10 min at 6 5% of maximal O-2 uptake while being infused with either Intralipid and hep arin (Int) or saline (control). Muscle biopsies were taken at 0, 1 (rest-to -exercise transition), 10, and 20 min. Exercise plasma FFA were elevated (0 .99 +/- 0.11 vs. 0.33 +/- 0.03 mM), and the respiratory exchange ratio was reduced during Int (0.87 +/- 0.02) vs. control (0.91 +/- 0.01). PDH activat ion was lower during Int at 1 min (1.33 +/- 0.19 vs. 2.07 +/- 0.14 mmol min (-1) kg(-1) wet muscle) and throughout exercise. Muscle pyruvate was reduce d during Int at rest [0.17 +/- 0.03 vs. 0.25 +/- 0.03 mmol/kg dry muscle (d m)] but increased above control during exercise. NADH was higher during Int vs. control at rest and 1 min of exercise (0.122 +/- 0.016 vs. 0.102 +/- 0 .005 and 0.182 +/- 0.016 vs. 0.150 +/- 0.016 mmol/kg dm), but not at 10 and 20 min. M-CoA was lower during Int vs. control at rest and 20 min of exerc ise (1.12 +/- 0.22 vs. 1.43 +/- 0.17 and 1.33 +/- 0.16 vs. 1.84 +/- 0.17 mu mol/kg dm). The reduced PDH activation with elevated FFA during the restto -exercise transition was related to higher mitochondrial NADH at rest and 1 min of exercise and lower muscle pyruvate at rest. The decreased M-CoA may have increased fat oxidation during exercise with elevated FFA by reducing carnitine palmitoyltransferase I inhibition and increasing mitochondrial F FA transport.