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

Eur J Appl Physiol. 2007 Mar;99(5):485-93. doi: 10.1007/s00421-006-0376-5. Epub 2006 Dec 22.


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-1alpha 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-1alpha 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Cell Line
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Fatty Acids, Nonesterified / blood*
  • Fatty Acids, Nonesterified / pharmacology
  • Gene Expression* / drug effects
  • Glycerol / blood
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Hypolipidemic Agents / administration & dosage
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics*
  • Male
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Physical Endurance / genetics*
  • Physical Endurance / physiology
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Pyrazines / administration & dosage
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Rats
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Uncoupling Protein 3


  • Fatty Acids, Nonesterified
  • Heat-Shock Proteins
  • Hypolipidemic Agents
  • Ion Channels
  • Mitochondrial Proteins
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • Pyrazines
  • RNA, Messenger
  • RNA-Binding Proteins
  • Transcription Factors
  • UCP3 protein, human
  • Ucp3 protein, rat
  • Uncoupling Protein 3
  • Carnitine O-Palmitoyltransferase
  • Protein Kinases
  • pyruvate dehydrogenase kinase 4
  • acipimox
  • Glycerol