Effects of reduced free fatty acid availability on skeletal muscle PDH activation during aerobic exercise. Pyruvate dehydrogenase

Am J Physiol Endocrinol Metab. 2003 Mar;284(3):E589-96. doi: 10.1152/ajpendo.00418.2002. Epub 2002 Nov 12.


This study investigated the effect of reduced free fatty acid (FFA) availability on pyruvate dehydrogenase activation (PDHa) and carbohydrate metabolism during moderate aerobic exercise. Eight active male subjects cycled for 40 min at 55% Vo(2 peak) on two occasions. During one trial, subjects ingested 20 mg/kg body mass of the antilipolytic drug nicotinic acid (NA) during the hour before exercise to reduce FFA. Nothing was ingested in the control trial (CON). Blood and expired gas measurements were obtained throughout the trials, and muscle biopsy samples were obtained immediately before exercise and at 5, 20, and 40 min of exercise. Plasma FFA were lower in the NA trial (0.13 +/- 0.01 vs. 0.48 +/- 0.03 mM, P < 0.05), and the respiratory exchange ratio (RER) was increased with NA (0.93 +/- 0.01 vs. 0.89 +/- 0.01, P < 0.05), resulting in a 14.5 +/- 1.8% increase in carbohydrate oxidation compared with CON. PDHa increased rapidly in both trials at exercise onset but was approximately 15% higher (P < 0.05) throughout exercise in the NA trial (2.44 +/- 0.19 and 2.07 +/- 0.12 mmol x kg wet muscle(-1) x min(-1) for NA and CON at 40 min). Muscle glycogenolysis was 15.3 +/- 9.6% greater in the NA trial vs. the CON trial but did not reach statistical significance. Glucose 6-phosphate contents were elevated (P < 0.05) in the NA trial at 30 and 40 min of exercise, but pyruvate and lactate contents were unaffected. These data demonstrate that the reduction of exogenous FFA availability increased the activation of PDH and carbohydrate oxidation during moderate aerobic exercise in men. The increased activation of PDH was not explained by changes in muscle pyruvate or the ATP/ADP ratio but may be related to a decrease in the NADH/NAD(+) ratio or an epinephrine-induced increase in calcium concentration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Availability
  • Enzyme Activation
  • Exercise / physiology*
  • Fatty Acids, Nonesterified / blood*
  • Humans
  • Ketone Oxidoreductases / blood
  • Ketone Oxidoreductases / metabolism*
  • Male
  • Muscle, Skeletal / enzymology*


  • Fatty Acids, Nonesterified
  • Ketone Oxidoreductases
  • pyruvate dehydrogenase (NADP+)