Xiaolin Wang1, Yan Lu1, E Wang1, Zhijian Zhang1, Xuelian Xiong1, Huijie Zhang2, Jieli Lu1, Sheng Zheng1, Jian Yang1, Xuefeng Xia3, Shuyu Yang4, Xiaoying Li5. 1. 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. 2. Xiamen Diabetes Institute, Department of Endocrinology and Metabolism, The First Hospital of Xiamen, Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. 3. Genomic Medicine and Center for Diabetes Research, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX, USA. 4. 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. 5. 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.
Abstract
BACKGROUND & AIMS: 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. CONCLUSION: These findings reveal a novel role of estrogen in improving hepatosteatosis through upregulation of SHP expression.
BACKGROUND & AIMS: 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 obesemice. 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.
Authors: Adrianna Maurer; Jaimie L Ward; Kelsey Dean; Sandra A Billinger; Haixia Lin; Kelly E Mercer; Sean H Adams; John P Thyfault Journal: J Appl Physiol (1985) Date: 2020-08-27
Authors: Silvana Sidhom; Augusto Schneider; Yimin Fang; Samuel McFadden; Justin Darcy; Roshini Sathiaseelan; Allyson K Palmer; Frederik J Steyn; Johannes Grillari; John J Kopchick; Andrzej Bartke; Shadab Siddiqi; Michal M Masternak; Michael B Stout Journal: J Gerontol A Biol Sci Med Sci Date: 2021-04-30 Impact factor: 6.053
Authors: Brian T Palmisano; Lin Zhu; Bridget Litts; Andreanna Burman; Sophia Yu; Joshua C Neuman; Uche Anozie; Thao N Luu; Emery M Edington; John M Stafford Journal: Metabolites Date: 2021-05-20