The Region Specific Influence of Estradiol on In-Vivo Lipolysis in Subcutaneous Adipose Tissue in Overweight-to-Moderately-Obese Premenopausal Women

Abstract

Premenopausal women demonstrate preferential accumulation of adiposity in the gynoid region, a distribution which shifts towards the abdominal region after the menopausal transition. Although estrogen is implicated as a major player in determining body fat distribution the mechanisms behind estrogenic action(s) in adipose tissue of women are still unclear. The global aim of this project was to determine if local estrogen influences regional adiposity in premenopausal women. Specifically, we investigated the influence of local estradiol on adipose tissue lipolysis as well as estrogen receptor content and adipocyte size in abdominal and gluteal subcutaneous adipose tissue of overweight-to-moderately-obese premenopausal women. Eighteen overweight-to-moderately-obese Caucasian (CA, n=9) and African American (AA, n=9) women were recruited. Between 15 and 17 of these women took part in each of the three studies. We found the influence of estradiol on lipolysis to be adipose tissue depot specific and treatment dependent, with estradiol perfusion blunting the response to lipolytic stimulation under some conditions while potentiating this response in others. Furthermore, we found differences in abdominal and gluteal estrogen receptor alpha and estrogen receptor beta protein content, potentially revealing region specific actions of estrogen through these estrogen receptors in adipose tissue. Finally, we found racial differences in adipose tissue morphology, as indicated by variations in adipocyte diameter populations in CA and AA women (higher proportion of medium size adipocytes in abdominal and gluteal subcutaneous adipose tissue of CA and higher proportion of small adipocytes in gluteal region of AA) which could underlie the increased chronic disease risk in AA compared to CA women for a given body mass index (BMI). Our findings indicate depot specific influence of estradiol on lipid mobilization may play a role in the predominant gluteal-femoral body fat distribution of premenopausal women. It is possible that depot specific effects of estradiol may be a result of regional differences in estrogen receptor content. Racial divergence in adipocyte morphology is an adipose tissue characteristic potentially underlying differing disease risk between CA and AA women of similar BMI. The integration of these results provides insight towards a more complete understanding of regional adiposity in overweight-to-obese premenopausal women, but future studies must be conducted to uncover the interaction between estrogen receptor content and local estrogen action as well as the direct physiological consequences of these findings.