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Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph N1G 2W1; and Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
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 exercise. Seven men rested
for 30 min and cycled for 10 min at 40% and 10 min at 65% of maximal
O2 uptake while being infused with either Intralipid and
heparin (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 activation was lower during Int at
1 min (1.33 ± 0.19 vs. 2.07 ± 0.14 mmol · min
1 · kg1 wet
muscle) and throughout exercise. Muscle pyruvate was reduced during Int
at rest [0.17 ± 0.03 vs. 0.25 ± 0.03 mmol/kg dry muscle (dm)] 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 exercise (1.12 ± 0.22 vs.
1.43 ± 0.17 and 1.33 ± 0.16 vs. 1.84 ± 0.17 µmol/kg
dm). The reduced PDH activation with elevated FFA during the
rest-to-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 FFA transport.
mitochondria; pyruvate dehydrogenase kinase; pyruvate dehydrogenase phosphatase; pyruvate; NADH; carnitine palmitoyltransferase I activity; fat metabolism; pH
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