title: Reduction of diet-induced obesity in transgenic mice overexpressing uncoupling protein 3 in skeletal muscle.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Medicine and Clinical Science, Endocrinology and Metabolism, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Son
authors.forename: K
authors.initials: K
authors.lastname: Hosoda
authors.forename: K
authors.initials: K
authors.lastname: Ishihara
authors.forename: L
authors.initials: L
authors.lastname: Bevilacqua
authors.forename: H
authors.initials: H
authors.lastname: Masuzaki
authors.forename: T
authors.initials: T
authors.lastname: Fushiki
authors.forename: M E
authors.initials: ME
authors.lastname: Harper
authors.forename: K
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000375:Aging; D000821:Animal Feed; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers; D004032:Diet; D004038:Diet, Reducing; D005951:Glucose Tolerance Test; D007473:Ion Channels; D007700:Kinetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000235:genetics*; D010101:Oxygen Consumption; D000071247:Uncoupling Protein 3; D015431:Weight Loss
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3