AQP7 mediates postmenopausal lipogenesis in adipocytes through FSH-induced transcriptional crosstalk with AP-1 sites

Abstract Research Question Fat accumulation is present in most postmenopausal women, whereas the underlying mechanism remains unclear. Aquaporin 7 (AQP7) is the most important glycerol channel facilitating glycerol efflux in adipocytes. High circulating follicular-stimulation hormone (FSH) of postmenopausal women may play an independent role in regulation of the lipogenic effect of AQP7 in adipocytes. In this study, we explored the role of AQP7 in the pathophysiology of postmenopausal lipogenesis mediated by high levels of circulating FSH. Design Primary adipocytes from postmenopausal and childbearing women were analyzed. An in vivo postmenopausal animal model was established. AQP7 expression, lipid accumulation and glycerol concentration in adipocytes were measured. Luciferase reporter assay and chromatin immunoprecipitation were performed to identify transcriptional crosstalk in AQP7 promoter. Results We found that FSH down-regulated AQP7 expression and glycerol efflux function in mature adipocytes of postmenopausal women and ovariectomized (OVX) mice. In vitro, FSH inhibited lipid accumulation in primary cultured mature adipocytes in a dose-dependent manner and the mechanism was downregulating AQP7 expression via FSH receptor pathway. The effect of FSH on AQP7 in adipocytes was through activating cAMP-response-element binding (CREB) protein, which could bind to activator protein-1 (AP-1) sites in AQP7 promotor, and therefore inhibited the transcriptional activation elicited by c-Jun. Conclusions Downregulation of AQP7 by FSH mediated post-menopausal lipogenesis, and the role of FSH was based on binding competition for AP-1 sites between CREB and c-Jun.