title: Effects of high fat provision on muscle PDH activation and malonyl-CoA content in moderate exercise.
abstract: 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 O(2) 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). kg(-1) 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 micromol/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.
authors.affiliation: Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: L M
authors.initials: LM
authors.lastname: Odland
authors.forename: G J
authors.initials: GJ
authors.lastname: Heigenhauser
authors.forename: L L
authors.initials: LL
authors.lastname: Spriet
mesh_terms: D000328:Adult; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015444:Exercise / Q000502:physiology*; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000494:pharmacology; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D011659:Pulmonary Gas Exchange; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004041:Dietary Fats; D005217:Fat Emulsions, Intravenous; D011768:Pyruvate Dehydrogenase Complex; D012965:Sodium Chloride; D008316:Malonyl Coenzyme A; D019289:Pyruvic Acid; D006493:Heparin