title: Treatment with estrogen protects against ovariectomy-induced hepatic steatosis by increasing AQP7 expression.
abstract: Recent evidence has suggested that the marked decrease in ovarian secretion of estrogens in postmenopausal women may be associated with the development of non-alcoholic fatty liver disease. The present study aimed to elucidate the mechanisms by which low levels of estrogen induce fatty liver disease using an ovariectomized (OVX) mouse model and an in vitro cell model. A total of 24 female C57/BL6 mice were divided into four groups: Sham operation, sham operation plus subcutaneous implantation of tamoxifen (TAM), bilateral OVX, and OVX plus subcutaneous implantation of 17β-estradiol (E2). Marked hepatic steatosis and increased expression of lipogenic genes (acetyl‑CoA carboxylase, fatty acid synthase and glycerol-3-phosphate acyltransferase) was observed in the estrogen‑depleted mice (TAM and OVX groups), as compared with in the sham operation group. Treatment with E2 significantly improved hepatic steatosis by decreasing the expression of the aforementioned lipogenic genes. Furthermore, hepatic aquaporin 7 (AQP7) expression was decreased in the estrogen‑depleted mice, but was increased in the OVX + E2 treatment group, as compared with in the sham operation group. These results suggested an association between AQP7 and low estrogen‑induced hepatic steatosis. Subsequently, the functions of AQP7 in hepatic steatosis were investigated using an oleic acid‑induced HepG2 cell model of steatosis. Treatment with E2 alleviated lipid accumulation and decreased the expression of lipogenic genes in vitro; however, such effects were attenuated following transfection with AQP7 small interfering RNA. The present study suggested a mechanism by which low levels of estrogen induce fatty liver disease, and may provide useful information regarding the prevention and treatment of fatty liver disease in postmenopausal women.
authors.affiliation: Department of Reproductive Endocrinology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Reproductive Endocrinology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Xing
authors.affiliation: Department of Reproductive Endocrinology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Weihai
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Reproductive Endocrinology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shu
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000235:genetics*; D004195:Disease Models, Animal; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D010052:Ovariectomy; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C491927:Aqp7 protein, mouse; D020346:Aquaporins; D004967:Estrogens; D034741:RNA, Small Interfering