Human skeletal muscle pyruvate dehydrogenase activity during exercise with high FFA provision

This study examined the regulation of pyruvate dehydrogenase (PDH) activity during exercise with high free fatty acid (FFA) provision. Seven males cycled for 10 min at 40% VO2max and 10 min at 65% VO2max while infused with either Intralipid and heparin (INT) or saline (CON). Average plasma FFA concentration was elevated with INT (0.99 ± 0.09 vs. 0.33 ± 0.02 mM) and respiratory exchange ratio was reduced during INT (0.87 ± 0.02 vs. 0.91 ± 0.01). Muscle biopsies were taken at 0 and 1 min, to examine the rest to exercise transition, and also at 10 and 20 min. Activity of PDH in the active form (PDHa) was lower during INT at 1 min (1.90 ± 0.28 vs. 2.96 ± 0.20 mmol/min kg wet muscle) and throughout exercise. Muscle PCr, G6P, ATP, NAD, and blood lactate concentrations were unaffected by INT. Muscle pyruvate was reduced during INT at rest (0.17 ± 0.03 vs. 0.25 ± 0.03 mmol/kg dry muscle), but not different from CON throughout exercise. NADH was higher during INT at rest (0.123 ± 0.016 vs. 0.084 ± 0.014 mmol/kg dm) and 1 min of exercise (0.183 ± 0.016 vs. 0.150 ± 0.015 mmol/kg dm), but not different at 10 and 20 min. The mechanism for the high FFA-induced reduction in the transformation to PDHa during the transition from rest to exercise may be due to a lower muscle pyruvate content at rest and increased resting and 1 min mitochondrial NADH content.