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Brown Adipose Tissue Metabolism in Women is Dependent on Ovarian Status.

In rodents, loss of estradiol (E2 ) reduces brown adipose tissue (BAT) metabolic activity. Whether E2 impacts BAT activity in women is not known. BAT oxidative metabolism was measured in premenopausal (N=27, 35±9 years, body mass index (BMI) = 26.0±5.3 kg/m2 ) and postmenopausal (N=25, 51±8 years, BMI = 28.0±5.0 kg/m2 ) women at room temperature (RT) and during acute cold exposure using [11 C]-acetate with positron emission tomography coupled with computed tomography (PET/CT). BAT glucose uptake was also measured during acute cold exposure using 2-deoxy-2-[18 F]fluoro-D-glucose ([18 F]FDG). To isolate the effects of ovarian hormones from biological aging, measurements were repeated in a subset of premenopausal women (N=8, 40±4 years, BMI = 28.0±7.2 kg/m2 ) after 6 months of gonadotropin-releasing hormone agonist (GnRHAG ) therapy to suppress ovarian hormones. At RT, there was no difference in BAT oxidative metabolism between premenopausal (0.56±0.31. min-1 ) and postmenopausal women (0.63±0.28. min-1 ). During cold exposure, BAT oxidative metabolism (1.28±0.85 vs. 0.91±0.63. min-1 , P=0.03) and net BAT glucose uptake (84.4±82.5 vs. 29.7±31.4 nmol. g-1. min-1 , P<0.01) were higher in premenopausal than postmenopausal women. In premenopausal women who underwent GnRHAG , cold-stimulated BAT oxidative metabolism was reduced to a similar level (from 1.36±0.66. min-1 to 0.91±0.41. min-1 ) to that observed in postmenopausal women (0.91±0.63. min-1 ). These results provide the first evidence in humans that reproductive hormones are associated with BAT oxidative metabolism and suggest that BAT may be a target to attenuate age-related reduction in energy expenditure and maintain metabolic health in postmenopausal women.

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