Impact of UCP1 and β3AR gene polymorphisms on age-related changes in brown adipose tissue and adiposity in humans

Int J Obes (Lond). 2013 Jul;37(7):993-8. doi: 10.1038/ijo.2012.161. Epub 2012 Oct 2.


Background: Brown adipose tissue (BAT) is involved in the regulation of whole-body energy expenditure and adiposity. The activity and prevalence of BAT decrease with age in humans.

Objective: To examine the effects of single nucleotide polymorphisms of the genes for uncoupling protein 1 (UCP1) and β3-adrenergic receptor (β3AR), key molecules of BAT thermogenesis, on age-related decline of BAT activity and accumulation of body fat in humans.

Methods: One hundred ninety-nine healthy volunteers (20-72 years old (y.o.)) underwent fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) after 2-h cold exposure to assess BAT activity. The visceral and subcutaneous fat areas at the abdominal level were estimated from the CT images. They were genotyped for -3826 A/G polymorphism of the UCP1 gene and 64 Trp/Arg mutation of the β3AR gene.

Results: BAT was detected in 88 subjects out of 199 (44%), more in younger (30 y.o., 55%) than older subjects (>40 y.o., 15%). BAT prevalence of older subjects tended to be lower in the UCP1 G/G group than the A allele group (A/A and A/G), and also in the β3AR Arg allele group (Trp/Arg and Arg/Arg) than the Trp/Trp group. When compared subjects who had two or more base substitutions on the two genes (the 2-4 allele group) with those who had less than two base substitutions (the 0-1 allele group), BAT prevalence was comparable in younger subjects (62% vs 50%) but lower in older subjects (0% vs 24%, P<0.05). Visceral fat area of the 2-4 allele group was higher than that of the 0-1 allele group (P<0.05) in older subjects, but not in younger subjects.

Conclusion: UCP1 -3826 A/G and β3AR 64 Trp/Arg substitutions accelerate age-related decrease in BAT activity, and thereby may associate with visceral fat accumulation with age.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown* / diagnostic imaging
  • Adipose Tissue, Brown* / metabolism
  • Adiposity* / genetics
  • Adult
  • Aged
  • Aging / genetics
  • Aging / metabolism*
  • Arginine
  • Energy Metabolism
  • Female
  • Fluorodeoxyglucose F18
  • Healthy Volunteers
  • Humans
  • Ion Channels* / genetics
  • Ion Channels* / metabolism
  • Japan
  • Male
  • Middle Aged
  • Mitochondrial Proteins* / genetics
  • Mitochondrial Proteins* / metabolism
  • Polymorphism, Single Nucleotide / genetics
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals
  • Receptors, Adrenergic, beta-3* / genetics
  • Receptors, Adrenergic, beta-3* / metabolism
  • Thermogenesis / genetics
  • Tomography, X-Ray Computed*
  • Tryptophan
  • Uncoupling Protein 1


  • Ion Channels
  • Mitochondrial Proteins
  • Radiopharmaceuticals
  • Receptors, Adrenergic, beta-3
  • UCP1 protein, human
  • Uncoupling Protein 1
  • Fluorodeoxyglucose F18
  • Tryptophan
  • Arginine