Brown Adipose Tissue Volume and Distribution in Premenopausal and Postmenopausal Women

Abstract

Introduction The loss of ovarian function and the accompanying decrease in estradiol during menopause has an impact on the metabolic activity of many tissues and organs, resulting in a reduction in resting energy expenditure. In rodents, ovariectomy or the absence of the estrogen receptor α suppresses brown adipose tissue (BAT) thermogenesis. It is therefore hypothesized that a reduction in BAT volume and thermogenesis may contribute to the reduction in resting energy expenditure in postmenopausal women. Objective The primary aim was to investigate the impact of estrogen on BAT volume and its distribution across the various depots in pre- and postmenopausal women. Methods A cohort of 22 premenopausal (33 years, 95% CI: 29 to 37 years) and 22 postmenopausal women (63 years, 95% CI: 60 to 67 years) took part in a 3-hr cold exposure using a liquid-conditioned suit perfused with 18°C water. During cold exposure, an i.v. bolus of [11C]-acetate and [18F]FDG were given sequentially, with each injection followed by a 30 min list-mode dynamic PET acquisition to quantify BAT oxidative metabolism and glucose uptake, respectively. Finally, a whole-body static PET acquisition was performed to quantify the whole-body biodistribution of glucose and estimate BAT volume and the distribution of this BAT volume across the various depots. BAT volume was determined according to the following criteria: [18F]FDG ≥ 2 SUVmean and a radiodensity between -10 and -250 HU. Results There was significant variability in BAT volume and its distribution in both pre- and postmenopausal women. Premenopausal women had greater total BAT volume (53 mL, 95% CI: 34 to 72 mL) compared to postmenopausal women (21 mL, 95% CI: 8 to 34 mL, P = 0.006), although both groups included individuals with undetectable BAT. In premenopausal women, 65% of BAT was localized in the supraclavicular depot (95% CI: 57 to 73%) and 9% in the paravertebral depot (95% CI: 5 to 13%), with the remaining depots (e.g. cervical, axillary, mediastinal, and perirenal) accounting for 25% (95% CI: 16 to 34%). In postmenopausal women, 45% of BAT was localized in the supraclavicular depot (95% CI: 24 to 66%) while the paravertebral depot represented 32% (95% CI: 12 to 52%) of total BAT. The remaining 23% (95% CI: 5 to 41 %) was distributed among the other depots. Thus, in postmenopausal women, there was a 20% reduction in the relative contribution of supraclavicular depots to the total volume and a 23% increase in the relative contribution of paravertebral depots to the total BAT volume compared to premenopausal women. Conclusion Here we show that total BAT volume is lower in postmenopausal women and results in a redistribution of BAT. However, there was tremendous variability in both BAT volume and distribution in both premenopausal and postmenopausal women. Further, it is difficult to distinguish the effects of estrogen from the effect of age or adiposity in the observed differences between our two cohorts.