Identification of functional estrogen response elements in glycerol channel Aquaporin-7 gene

Objective: We previously reported that tissue-specific effects of estrogen on Aquaporin-7 (AQP7) expression are associated with the development of menopausal obesity. The current study was designed to identify the estrogen response elements (EREs) in the promoter of Aqp7 and investigate the role of AQP7 in the regulation of estrogen-induced anti-adipogenesis. Methods: We measured AQP7 expression and intracellular fat accumulation in 3T3-L1 adipocytes either silenced with shRNA or treated with estrogen receptor (ER)-specific antagonists or agonists before exposure to estrogen. EREs were predicted by Bioinformatics, assessed by chromatin immunoprecipitation, and verified by luciferase reporter assay. Results: We found that regulation of AQP7 expression was mainly via ERα, as confirmed by the use of ER selective antagonists and agonists. In addition, the induction of AQP7 expression by estrogen was linked to ER binding with two EREs in the promoter region of Aqp7. Furthermore, we found that the regulation of adipogenesis by 17β-estradiol was AQP7 dependent, as evidenced by the increase in fat accumulation after silencing AQP7. Conclusions: Estrogen induces AQP7 expression by binding EREs in the promoter of the Aqp7 gene, resulting in fat catabolism of adipocyte. These results provide new insights into the molecular mechanisms underpinning the anti-adipogenic effect of estrogen.