title: Hepatic estrogen receptor α improves hepatosteatosis through upregulation of small heterodimer partner.
abstract: OBJECTIVE
  Estrogen participates in the control of energy homeostasis and lipid metabolism. However the role of hepatic estrogen receptor α (ERα) in triglyceride (TG) homeostasis remains poorly understood. This study aims to investigate the roles of estrogen and ERα in the regulation of hepatic TG metabolism.
  
  
  METHODS
  Liver TG metabolism was analyzed in female mice with ovariectomy or tamoxifen treatment, and in hepatic ERα knockdown or overexpression. Phenotypes and expression of genes were compared in male and female mice with farnesoid X receptor deficiency. The mechanism of ERα 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 ERα using adenoviral shRNA markedly increased hepatic TG accumulation, while overexpression of ERα 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.
  
  
  CONCLUSIONS
  These findings reveal a novel role of estrogen in improving hepatosteatosis through upregulation of SHP expression.
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Xiamen Diabetes Institute, Department of Endocrinology and Metabolism, The First Hospital of Xiamen, Xiamen University, 55 Zhenhai Road, Xiamen 361003, China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jieli
authors.initials: J
authors.lastname: Lu
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Genomic Medicine and Center for Diabetes Research, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xia
authors.affiliation: Xiamen Diabetes Institute, Department of Endocrinology and Metabolism, The First Hospital of Xiamen, Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Electronic address: xmyangshuyu@126.com.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; The Key Laboratory of Endocrine Tumors and the Division of Endocrine and Metabolic Diseases, E-Institute of Shanghai Universities, Shanghai 200025, China; Chinese-French Laboratory of Genomics and Life Sciences, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: lixy@sibs.ac.cn.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics*; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D004247:DNA
keywords: ERα; Estrogen; FXR; Hepatosteatosis; SHP