Reduction of diet-induced obesity in transgenic mice overexpressing uncoupling protein 3 in skeletal muscle

Diabetologia. 2004 Jan;47(1):47-54. doi: 10.1007/s00125-003-1272-8. Epub 2003 Dec 12.

Abstract

Aims/hypothesis: It has been suggested that uncoupling protein 3 (UCP3) can increase energy expenditure, thereby regulating body weight. Although studies on UCP3 knock-out mice suggest that lack of UCP3 function does not cause obesity or Type 2 diabetes, it is possible that up-regulation of UCP3 function improves these disorders or their clinical sequelae. A 10- to 20-fold increase of UCP3 gene expression is achievable through physiological or pharmacological stimuli. We examined the phenotype of transgenic mice with approximately 18-fold overexpression of mouse UCP3 mRNA in skeletal muscle.

Methods: We generated transgenic mice with approximately 18-fold overexpression of mouse UCP3 mRNA in skeletal muscle under control of the skeletal muscle-specific muscle creatine kinase gene promoter. The phenotype of these mice was analysed either on a standard diet or on a 4-week high-fat diet.

Results: In mice on standard chow, there was no difference in body weight, oxygen consumption and mitochondrial protonmotive force between transgenic mice and non-transgenic littermates. However, transgenic mice tended to have lower body weight, increased oxygen consumption and decreased mitochondrial protonmotive force than the control mice. Transgenic mice on a 4-week high-fat diet consumed much more oxygen and had noticeably less weight gain and less epididymal fat, as well as better glucose tolerance than non-transgenic littermates.

Conclusions/interpretation: Our study shows that 18-fold overexpression of UCP3 mRNA in the skeletal muscle reduced diet-induced obesity. An 18-fold increase of UCP3 mRNA can be attained by physiological or pharmacological stimuli, suggesting that UCP3 has therapeutic potential in the treatment of obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animal Feed
  • Animals
  • Base Sequence
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • DNA Primers
  • Diet*
  • Diet, Reducing
  • Glucose Tolerance Test
  • Ion Channels
  • Kinetics
  • Male
  • Mice
  • Mice, Transgenic
  • Mitochondria, Muscle / metabolism*
  • Mitochondrial Proteins
  • Muscle, Skeletal / metabolism*
  • Obesity / genetics*
  • Oxygen Consumption
  • Uncoupling Protein 3
  • Weight Loss

Substances

  • Carrier Proteins
  • DNA Primers
  • Ion Channels
  • Mitochondrial Proteins
  • Ucp3 protein, mouse
  • Uncoupling Protein 3