Low Muscle Glycogen and Elevated Plasma Free Fatty Acid Modify but Do Not Prevent Exercise-Induced PDH Activation in Human Skeletal Muscle
- Kristian Kiilerich1,2,3,
- Mikkel Gudmundsson1,2,3,
- Jesper B. Birk1,4,
- Carsten Lundby1,5,
- Sarah Taudorf1,2,6,
- Peter Plomgaard1,2,6,
- Bengt Saltin1,5,
- Per A. Pedersen3,
- Jorgen F.P. Wojtaszewski1,4 and
- Henriette Pilegaard1,2,3
- 1Copenhagen Muscle Research Centre, University of Copenhagen, Copenhagen, Denmark;
- 2Centre of Inflammation and Metabolism, University of Copenhagen, Copenhagen, Denmark;
- 3Department of Biology, University of Copenhagen, Copenhagen, Denmark;
- 4Section of Human Physiology, Department of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark;
- 5Rigshospitalet, Section 7652, Copenhagen, Denmark;
- 6Rigshospitalet, Section 7641, Copenhagen, Denmark.
- Corresponding author: Kristian Kiilerich, kkiilerich{at}bio.ku.dk.
Abstract
OBJECTIVE To test the hypothesis that free fatty acid (FFA) and muscle glycogen modify exercise-induced regulation of PDH (pyruvate dehydrogenase) in human skeletal muscle through regulation of PDK4 expression.
RESEARCH DESIGN AND METHODS On two occasions, healthy male subjects lowered (by exercise) muscle glycogen in one leg (LOW) relative to the contra-lateral leg (CON) the day before the experimental day. On the experimental days, plasma FFA was ensured normal or remained elevated by consuming breakfast rich (low FFA) or poor (high FFA) in carbohydrate, 2 h before performing 20 min of two-legged knee extensor exercise. Vastus lateralis biopsies were obtained before and after exercise.
RESULTS PDK4 protein content was ∼2.2- and ∼1.5-fold higher in LOW than CON leg in high FFA and low FFA, respectively, and the PDK4 protein content in the CON leg was approximately twofold higher in high FFA than in low FFA. In all conditions, exercise increased PDHa (PDH in the active form) activity, resulting in similar levels in LOW leg in both trials and CON leg in high FFA, but higher level in CON leg in low FFA. PDHa activity was closely associated with the PDH-E1α phosphorylation level.
CONCLUSIONS Muscle glycogen and plasma FFA attenuate exercise-induced PDH regulation in human skeletal muscle in a nonadditive manner. This might be through regulation of PDK4 expression. The activation of PDH by exercise independent of changes in muscle glycogen or plasma FFA suggests that exercise overrules FFA-mediated inhibition of PDH (i.e., carbohydrate oxidation), and this may thus be one mechanism behind the health-promoting effects of exercise.
Footnotes
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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.
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- Received July 15, 2009.
- Accepted October 2, 2009.
- © 2010 American Diabetes Association
