Impact of Age on the Relationships of Brown Adipose Tissue With Sex and Adiposity in Humans

Abstract

OBJECTIVEBrown adipose tissue (BAT) regulates energy homeostasis and fat mass in mammals and newborns and, most likely, in adult humans. Because BAT activity and BAT mass decline with age in humans, the impact of BAT on adiposity may decrease with aging. In the present study we addressed this hypothesis and further investigated the effect of age on the sex differences in BAT activity and BAT mass.RESEARCH DESIGN AND METHODSData from 260 subjects (98 with BAT and 162 study date–matched control subjects) who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body.RESULTSBAT activity and BAT mass were higher in female (1.59 ± 0.10 and 32 ± 5 g vs. 1.02 ± 0.10 and 18 ± 4 g, both P ≤ 0.0006) than in male subjects. In multivariate analyses, sex (P < 0.0001), age (P < 0.0001), and BMI (P = 0.0018) were associated independently with BAT activity. Interestingly, only in male subjects was there an interaction between BMI and age in determining BAT activity (P = 0.008) and BAT mass (P = 0.0002); BMI decreased with increasing BAT activity and BAT mass in the lowest age tertile (Spearman rank correlation coefficient rs = −0.38, P = 0.015 and rs = −0.37, P = 0.017, respectively), not in the higher age tertiles. Furthermore, BAT activity and mass differed between female and male subjects only in the upper two age tertiles (all P ≤ 0.09).CONCLUSIONSOur data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects.

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

“…A significant decrease in thermogenesis in BAT and browning of WAT has been described as a result of increased age in humans and rodents (Florez‐Duquet, Horwitz, & McDonald, 1998; Pfannenberg et al, 2010; Yoneshiro et al, 2011). We therefore examined the effects of cold exposure in Postn ‐knockout mice and observed a rapid loss of body weight within 72 hr of cold exposure which prevented further long‐term treatments (Figure 3a,b).…”

UCP1 genetic polymorphism (–3826 A/G) diminishes resting energy expenditure and thermoregulatory sympathetic nervous system activity in young females

“…Conversely, agerelated decline in BAT activity was also demonstrated. 1,5,26 Our subjects were young and almost all were lean; therefore, the impact of UCP1 gene polymorphism on REE may be greater than that in other age groups. Long-term study is needed to investigate the impact of the G allele of the UCP1 gene on future weight gain in females around menopause; 27 moreover, studies including male subjects of various ages are required.…”

Cold but not sympathomimetics activates human brown adipose tissue in vivo

“…Multiple recent studies have shown that adult humans have functional BAT that can be activated in response to cold exposure in a process called nonshivering thermogenesis (1)(2)(3)(4). In both small and large population studies (1,2,4,5), there is an inverse correlation between BAT activity and obesity, suggesting that activating BAT, through pharmacological, environmental, or potentially nutritional interventions, could become a therapeutic means to treat obesity and diabetes. Indeed, human BAT energy expenditure may be a critical counterbalance to the weight gain and metabolic dysregulation caused by excess energy storage in white adipose tissue.…”