Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo

J Clin Invest. 2003 Feb;111(4):479-86. doi: 10.1172/JCI16653.


Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (LF) or high-fat (HF) diets. Immediately following exercise, blood flow was reinstated, and muscle was sampled after 20, 60, and 120 seconds of recovery. Mitochondrial coupling was assessed by determining the rate of PCr resynthesis during recovery. The HF diet increased UCP3 protein content by approximately 44% compared with the LF diet. However, this HF diet-induced increase in UCP3 expression was not associated with any changes in the rate of muscle PCr resynthesis during conditions of maximal flux through oxidative phosphorylation. Muscle acetylcarnitine, free-creatine, and lactate concentrations during recovery were unaffected by the HF diet. Taken together, our findings demonstrate that increasing muscle UCP3 expression does not diminish the rate of PCr resynthesis, allowing us to conclude that the primary role of UCP3 in humans is not uncoupling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carrier Proteins / metabolism*
  • Creatine / metabolism
  • Dietary Fats / administration & dosage
  • Fatty Acids / metabolism
  • Humans
  • Ion Channels
  • Lactic Acid / metabolism
  • Male
  • Mitochondria, Muscle / metabolism*
  • Mitochondrial Proteins
  • Muscle Contraction / physiology
  • Muscle, Skeletal / metabolism*
  • Oxidative Phosphorylation
  • Phosphocreatine / biosynthesis
  • Proton-Translocating ATPases / metabolism
  • Uncoupling Agents / metabolism
  • Uncoupling Protein 3


  • Carrier Proteins
  • Dietary Fats
  • Fatty Acids
  • Ion Channels
  • Mitochondrial Proteins
  • UCP3 protein, human
  • Uncoupling Agents
  • Uncoupling Protein 3
  • Phosphocreatine
  • Lactic Acid
  • Proton-Translocating ATPases
  • Creatine