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Reduced plasma free fatty acid availability during exercise: effect on gene expression

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Abstract

Endurance exercise transiently increases the mRNA of key regulatory proteins involved in skeletal muscle metabolism. During prolonged exercise and subsequent recovery, circulating plasma fatty acid (FA) concentrations are elevated. The present study therefore aimed to determine the sensitivity of key metabolic genes to FA exposure, assessed in vitro using L6 myocytes and secondly, to measure the expression of these same set of genes in vivo, following a single exercise bout when the post-exercise rise in plasma FA is abolished by acipimox. Initial studies using L6 myotubes demonstrated dose responsive sensitivity for both PDK4 and PGC-1α mRNA to acute FA exposure in vitro. Nine active males performed two trials consisting of 2 h exercise, followed by 2 h of recovery. In one trial, plasma FA availability was reduced by the administration of acipimox (LFA), a pharmacological inhibitor of adipose tissue lipolysis, and in the second trial a placebo was provided (CON). During the exercise bout and during recovery, the rise in plasma FA and glycerol was abolished by acipimox treatment. Following exercise the mRNA abundance of PDK4 and PGC-1α were elevated and unaffected by either acipimox or placebo. Further analysis of skeletal muscle gene expression demonstrated that the CPT I gene was suppressed in both trials, whilst UCP-3 gene was only modestly regulated by exercise alone. Acipimox ingestion did not alter the response for both CPT I and UCP-3. Thus, this study demonstrates that the normal increase in circulating concentrations of FA during the later stages of exercise and subsequent recovery is not required to induce skeletal muscle mRNA expression of several proteins involved in regulating substrate metabolism.

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Acknowledgments

We gratefully acknowledge the enthusiastic support of the subjects who volunteered to participate in these trials. We would also like to thank Ms Janelle Mollica for technical assistance. Dr van Loon was supported by a grant from the Netherlands Organization for Scientific Research (NWO).

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Authors and Affiliations

  1. School of Exercise and Nutritional Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC, 3125, Australia

    Rebecca J. Tunstall & David Cameron-Smith

  2. Department of Medicine, University of Adelaide, Adelaide, SA, 5005, Australia

    Andrew J. McAinch

  3. Department of Physiology, The University of Melbourne, Melbourne, VIC, 3010, Australia

    Mark Hargreaves

  4. Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, 6200 MD Maastricht, The Netherlands

    Luc J. C. van Loon

Authors
  1. Rebecca J. Tunstall
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  2. Andrew J. McAinch
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  3. Mark Hargreaves
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  4. Luc J. C. van Loon
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  5. David Cameron-Smith
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Correspondence to David Cameron-Smith.

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Tunstall, R.J., McAinch, A.J., Hargreaves, M. et al. Reduced plasma free fatty acid availability during exercise: effect on gene expression. Eur J Appl Physiol 99, 485–493 (2007). https://doi.org/10.1007/s00421-006-0376-5

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