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

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 beta 3-adrenergic receptor (beta 3AR), 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 beta 3AR 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 beta 3AR 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 beta 3AR 64 Trp/Arg substitutions accelerate age-related decrease in BAT activity, and thereby may associate with visceral fat accumulation with age.