SAT-650 - Mechanisms by Which Estrous Cycles Influence Beige Fat Appearance

Across the female menstrual cycle, dynamic shifts in energy expenditure, insulin sensitivity, lipid metabolism, and basal body temperature occur in accordance with the rise and fall of estradiol. Estradiol affects multiple reproductive and non-reproductive tissues, including white adipose tissue (WAT). Many female-specific differences in WAT distribution and function are attributed to the effect of estrogens on WAT. Premenopausal women typically store fat in the more metabolically favorable subcutaneous WAT (sWAT) depot compared to men, and postmenopausal women, who tend to accumulate more central and visceral WAT. As such, there remains a critical need to understand how reproductive cycles affect adipose tissue dynamics to not only clarify sex-specific differences in energy balance and insulin sensitivity but also reduce the metabolic and cardiovascular disease risks that accompany the menopausal transition. My analysis of sWAT in wild-type mice during the mouse estrous cycle revealed morphological changes in adipocyte size, the presence of multilocular adipocytes, and alterations in beige fat gene expression around the time of ovulation. We find that these observations are conserved across mouse strains but are not observed in mice of increased reproductive age. It is well understood that the amount of thermogenic beige adipocytes in sWAT corresponds with insulin sensitivity and protection against the comorbidities of obesity and cardiovascular disease. Therefore, we hypothesize that estrous cycles regulate beige adipocyte emergence and influence whole-body energy balance to promote ovulation. In support of this hypothesis, we find that mice lacking UCP1, the canonical beige fat marker, are sub-fertile with abnormal estrous cycles and smaller litter sizes. Additionally, our studies using the triple beta-adrenergic receptor knockout mouse model (Adrb1, Adrb2, Adrb3) demonstrate that the beta-adrenergic pathway is involved in the adipocyte dynamics we observe during the estrous cycle. Importantly, this research represents a crucial step towards detailing WAT responses to estrous cycles and defining why the loss of estrous cycling results in an elevated risk for metabolic disorders, including type 2 diabetes and cardiovascular disease.

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