Hepatic estrogen receptor α improves hepatosteatosis through upregulation of small heterodimer partner
Hepatic estrogen receptor α improves hepatosteatosis through upregulation of small heterodimer partner
复制标题
肝脏雌激素受体α通过小异二聚体伴侣的上调改善肝脂肪变性
DOI：
10.1016/j.jhep.2015.02.029
复制
发表时间：
2015-07-01
影响因子：
25.7
通讯作者：
Li, Xiaoying
中科院分区：
文献类型：
--
作者：
Wang, Xiaolin;Lu, Yan;Li, Xiaoying
背景与目的：雌激素参与能量稳态和脂代谢的调节。然而，肝脏雌激素受体α(ERα)在甘油三酯(TG)稳态中的作用仍然知之甚少。本研究旨在探讨雌激素和ERα在肝脏TG代谢调节中的作用。方法：对去卵巢或三苯氧胺处理的雌性小鼠肝脏TG代谢进行分析，并对肝脏ERα基因敲除或过表达进行分析。比较了雄性和雌性法尼类X受体缺陷小鼠的表型和基因表达。结果：去卵巢或三苯氧胺治疗的雌性小鼠肝组织中均有甘油三酯的蓄积。用腺病毒shRNA去除ERα可显著增加肝脏TG蓄积，而过表达ERα可改善肥胖小鼠的肝脏骨质疏松症。在分子水平上，雌激素通过与其近端启动子结合而上调肝脏SHP的表达。此外，在SHP缺乏的小鼠中，雌激素的作用在很大程度上被削弱。结论：这些发现揭示了雌激素通过上调SHP的表达而改善肝骨病的新作用。(C)2015年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background & Aims: Estrogen participates in the control of energy homeostasis and lipid metabolism. However the role of hepatic estrogen receptor alpha (ER alpha) in triglyceride (TG) homeostasis remains poorly understood. This study aims to investigate the roles of estrogen and ER alpha in the regulation of hepatic TG metabolism.Methods: Liver TG metabolism was analyzed in female mice with ovariectomy or tamoxifen treatment, and in hepatic ER alpha knockdown or overexpression. Phenotypes and expression of genes were compared in male and female mice with farnesoid X receptor deficiency. The mechanism of ER alpha in the regulation of small heterodimer partner (SHP) expression was further investigated.Results: Female mice receiving ovariectomy or tamoxifen treatment exhibited hepatic TG accumulation. Ablation of ER alpha using adenoviral shRNA markedly increased hepatic TG accumulation, while overexpression of ER alpha ameliorated hepatosteatosis in obese mice. At the molecular level, estrogen upregulated hepatic SHP expression through binding to its proximal promoter. In addition, the roles of estrogen were largely blunted in mice with SHP deficiency.Conclusion: These findings reveal a novel role of estrogen in improving hepatosteatosis through upregulation of SHP expression. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.