PDH-E1α Dephosphorylation and Activation in Human Skeletal Muscle During Exercise

Effect of Intralipid Infusion

  1. Henriette Pilegaard123,
  2. Jesper B. Birk14,
  3. Massimo Sacchetti15,
  4. Marina Mourtzakis16,
  5. D. Graham Hardie7,
  6. Greg Stewart7,
  7. P. Darrell Neufer8,
  8. Bengt Saltin15,
  9. Gerrit van Hall125 and
  10. Jorgen F.P. Wojtaszewski14
  1. 1Copenhagen Muscle Research Centre, Copenhagen, Denmark
  2. 2Centre of Inflammation and Metabolism, Copenhagen, Denmark
  3. 3Institute of Molecular Biology and Physiology, The August Krogh Building, University of Copenhagen, Copenhagen, Denmark
  4. 4Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
  5. 5Rigshospitalet Section 7652, Copenhagen, Denmark
  6. 6Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
  7. 7Division of Molecular Physiology, School of Life Sciences, Dundeee University, Dundee, Scotland, U.K
  8. 8John B. Pierce Laboratory, Cellular and Molecular Physiology, Yale University, New Haven, Connecticut
  1. Address correspondence and reprint requests to Henriette Pilegaard, PhD, August Krogh Building, Universitetsparken 13, 2100 Copenhagen Ø, Denmark. E-mail: hpilegaard{at}aki.ku.dk

Abstract

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.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted August 11, 2006.
    • Received February 1, 2006.
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