Gudiksen 2015 Abstract MiPschool Greenville 2015

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IL-6 modulates regulation of PDH during acute prolonged exercise.


Gudiksen A, Schwartz C, Bertholdt L, Knudsen JG, Pilegaard H (2015)

Event: MiPschool Greenville 2015

Skeletal muscle substrate utilization switch from carbohydrate towards fat during prolonged exercise as substrate availability is altered. Pyruvate dehydrogenase (PDH), which represents the only entry point for CHO-derived substrates into the mitochondria for oxidation, has been suggested to be pivotal in the transition between fuels [1]. IL-6 is produced in skeletal muscle during exercise in a time- an intensity- dependent manner [2] and has been suggested to increase both fat oxidation and glucose uptake by indirect increases in AMPK activity [3]. IL-6 and AMPK have both been suggested to regulate PDH potentially through an IL-6-AMPK-PDH parthway [4]. Together this indicates a role for IL-6 in the regulation of PDH and maintenance of metabolic flexibility during prolonged exercise. The present study seeks to uncover the impact of skeletal muscle IL-6 on skeletal muscle PDH regulation during 2 hours of acute exercise.

IL-6 muscle-specific knockout (MKO) and floxed littermate mice underwent either 10 min, 1 hour or 2 hours of treadmill running. Trunk blood and quadriceps muscles were removed.

While glycogen decreased with exercise independent of genotype, intramuscular glucose only increased in controls and plasma lactate and plasma FFA decreased in both genotypes, but was lower in IL-6 MKO than controls at least at one time point suggesting that loss of skeletal muscle IL-6 influences substrate utilization. AMPK and ACC phosphorylation increased with exercise with no genotype differences indicating an exercise-induced AMPK and ACC regulation independent of IL-6. Exercise elicited a transient increase in PDHa activity only in controls and the PDHa activity was higher in MKO than control mice at rest and 60 min suggesting that muscle IL-6 reduces PDHa activity. PDH phosphorylationSer300 followed the overall dynamics of the PDHa activity, but revealed no genotype differences that could explain the observed PDH differences.

IL-6 modulates PDHa activity. The difference in PDHa activity cannot be explained by differences in AMPK or PDH phosphorylation and may thus be mediated by other posttranslational modifications.

Labels: MiParea: Exercise physiology;nutrition;life style 

Organism: Mouse  Tissue;cell: Skeletal muscle 

Event: Poster 


1-Section Mol Integrative Physiol, Dept Biology, Univ Copenhagen, Denmark. -

References and acknowledgements

  1. Hue L, Taegtmeyer H (2009) The Rande cycle revisited: a new head for an old hat. AM J Pysiol Endocrinol Metab 297:E578-91
  2. Fischer CP (2006) Interleukin-6 in acute exercise and training: what is the biological relevance? Exercise Immunol Rev 12:6-33.
  3. Kelly M, Keller C, Avilucea PR, Keller P, Luo Z, Xiang X, Giralt M, Hidalgo J, Saha AK, Pedersen BK, Ruderman NB (2004) AMPK activity is diminished in tissues of IL-6 KO mice: the effect of exercise. Biochem Biophys Res Commun 320:449-54.
  4. Klein DK, Pilegaard H, Treebak JT, Jensen TE, Viollet B, Schjerling P, Wojtaszewski JF (2007) Lack of AMPK alpha2 enhances pyruvate dehydrogenase activity during exercise. AM J Physiol Endocrinol Metab 293:E1242-9.