PDH-E1α Dephosphorylation and Activation in Human Skeletal Muscle During Exercise Journal Articles uri icon

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  • To investigate pyruvate dehydrogenase (PDH)-E1α subunit phosphorylation and whether free fatty acids (FFAs) regulate PDH activity, seven subjects completed two trials: saline (control) and intralipid/heparin (intralipid). Each infusion trial consisted of a 4-h rest followed by a 3-h two-legged knee extensor exercise at moderate intensity. During the 4-h resting period, activity of PDH in the active form (PDHa) did not change in either trial, yet phosphorylation of PDH-E1α site 1 (PDH-P1) and site 2 (PDH-P2) was elevated in the intralipid compared with the control trial. PDHa activity increased during exercise similarly in the two trials. After 3 h of exercise, PDHa activity remained elevated in the intralipid trial but returned to resting levels in the control trial. Accordingly, in both trials PDH-P1 and PDH-P2 decreased during exercise, and the decrease was more marked during intralipid infusion. Phosphorylation had returned to resting levels at 3 h of exercise only in the control trial. Thus, an inverse association between PDH-E1α phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1α phosphorylation, but exercise overrules this effect of FFA on PDH-E1α phosphorylation leading to even greater dephosphorylation during exercise with intralipid infusion than with saline.


  • Pilegaard, Henriette
  • Birk, Jesper B
  • Sacchetti, Massimo
  • Mourtzakis, Marina
  • Hardie, D Graham
  • Stewart, Greg
  • Neufer, P Darrell
  • Saltin, Bengt
  • van Hall, Gerrit
  • Wojtaszewski, Jorgen FP

publication date

  • November 1, 2006