Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean

Nature. 2000 Jul 27;406(6794):415-8. doi: 10.1038/35019082.


Uncoupling protein-3 (UCP-3) is a recently identified member of the mitochondrial transporter superfamily that is expressed predominantly in skeletal muscle. However, its close relative UCP-1 is expressed exclusively in brown adipose tissue, a tissue whose main function is fat combustion and thermogenesis. Studies on the expression of UCP-3 in animals and humans in different physiological situations support a role for UCP-3 in energy balance and lipid metabolism. However, direct evidence for these roles is lacking. Here we describe the creation of transgenic mice that overexpress human UCP-3 in skeletal muscle. These mice are hyperphagic but weigh less than their wild-type littermates. Magnetic resonance imaging shows a striking reduction in adipose tissue mass. The mice also exhibit lower fasting plasma glucose and insulin levels and an increased glucose clearance rate. This provides evidence that skeletal muscle UCP-3 has the potential to influence metabolic rate and glucose homeostasis in the whole animal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Animals, Genetically Modified
  • Blood Glucose / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Energy Metabolism
  • Female
  • Humans
  • Hyperphagia / genetics
  • Ion Channels
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • Mitochondrial Proteins
  • Muscle, Skeletal / physiology*
  • Phenotype
  • Thinness
  • Uncoupling Protein 3


  • Blood Glucose
  • Carrier Proteins
  • Ion Channels
  • Mitochondrial Proteins
  • UCP3 protein, human
  • Ucp3 protein, mouse
  • Uncoupling Protein 3