title: Comparative proteomic study reveals 17β-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease.
abstract: Nonalcoholic fatty liver disease (NAFLD) is characterized by a massive accumulation of lipid droplets (LDs). The aim of this study was to determine the function of 17β-hydroxysteroid dehydrogenase-13 (17β-HSD13), one of our newly identified LD-associated proteins in human subjects with normal liver histology and simple steatosis, in NAFLD development. LDs were isolated from 21 human liver biopsies, including 9 cases with normal liver histology (group 1) and 12 cases with simple steatosis (group 2). A complete set of LD-associated proteins from three liver samples of group 1 or group 2 were determined by 2D LC-MS/MS. By comparing the LD-associated protein profiles between subjects with or without NAFLD, 54 up-regulated and 35 down-regulated LD-associated proteins were found in NAFLD patients. Among them, 17β-HSD13 represents a previously unidentified LD-associated protein with a significant up-regulation in NAFLD. Because the 17β-HSD family plays an important role in lipid metabolism, 17β-HSD13 was selected for validating the proteomic findings and exploring its role in the pathogenesis of NAFLD. Increased hepatic 17β-HSD13 and its LD surface location were confirmed in db/db (diabetic) and high-fat diet-fed mice. Adenovirus-mediated hepatic overexpression of human 17β-HSD13 induced a fatty liver phenotype in C57BL/6 mice, with a significant increase in mature sterol regulatory element-binding protein 1 and fatty acid synthase levels. The present study reports an extensive set of human liver LD proteins and an array of proteins differentially expressed in human NAFLD. We also identified 17β-HSD13 as a pathogenic protein in the development of NAFLD.
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing, 100191, China;
authors.forename: Wen
authors.initials: W
authors.lastname: Su
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China;University of Chinese Academy of Sciences, Beijing, 100049, China;
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing, 100191, China;
authors.forename: Xiao
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Surgery, Peking University First Hospital, Beijing, 100044, China;
authors.forename: Wenhan
authors.initials: W
authors.lastname: Wu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China;
authors.forename: Linghai
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Surgery, Peking University First Hospital, Beijing, 100044, China;
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing, 100191, China;
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing, 100191, China;
authors.forename: Chunjiong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing, 100191, China;
authors.forename: Huamin
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing, 100191, China;
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing, 100191, China;
authors.forename: Qifei
authors.initials: Q
authors.lastname: Han
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China;University of Chinese Academy of Sciences, Beijing, 100049, China;
authors.forename: Shimeng
authors.initials: S
authors.lastname: Xu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China;
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Beijing Autopsy Center, Peking University, Beijing, 100191, China;Department of Pathology, Health Science Center and.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Physiology, Shenzhen University Health Science Center, Shenzhen, 518060, China; and.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; pliu@ibp.ac.cn jgustafsson@uh.edu youfeiguan@szu.edu.cn.
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204 pliu@ibp.ac.cn jgustafsson@uh.edu youfeiguan@szu.edu.cn.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing, 100191, China;Department of Physiology, Shenzhen University Health Science Center, Shenzhen, 518060, China; and pliu@ibp.ac.cn jgustafsson@uh.edu youfeiguan@szu.edu.cn.
authors.forename: Youfei
authors.initials: Y
authors.lastname: Guan
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000201:enzymology* / Q000473:pathology*; D022781:Hepatocytes / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008055:Lipids / Q000737:chemistry; D050155:Lipogenesis; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D015854:Up-Regulation
chemical_list: D008055:Lipids; D020543:Proteome; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase
keywords: HSDI7β13; SCDR9; lipogenesis