title: SUMO-specific protease 3 is a key regulator for hepatic lipid metabolism in non-alcoholic fatty liver disease.
abstract: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes. The role of SENP3 in lipid metabolism, particularly NAFLD, is unclear. Our results showed that hepatic SENP3 was up-regulated in NAFLD patients and an animal model in vivo and after loading hepatocytes with free fatty acids (FFA) in vitro. Intracellular lipid accumulation was determined in SENP3 silenced or overexpressed hepatocytes with/without FFA in vitro. Confirming a role for SENP3, gene silencing was associated in vitro with amelioration of lipid accumulation and overexpression with enhancement of lipid accumulation. SENP3 related genes in NAFLD were determined in vitro using RNA-Seq. Eleven unique genes closely associated with lipid metabolism were generated using bioinformatics. Three selected genes (apoe, a2m and tnfrsf11b) were verified in vitro, showing apoe, a2m and tnfrsf11b were regulated by SENP3 with FFA stimulation. Intrahepatic and circulating APOE, A2M and TNFRSF11B were elevated in NAFLD compared with controls. These data demonstrate the important role of SENP3 in lipid metabolism during the development of NAFLD via downstream genes, which may be useful information in the development of NAFLD. The precise role of SENP3 in NAFLD will be investigated using liver-specific conditional knockout mice in future studies.
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
authors.forename: Fudong
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Xiang
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Shaowen
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Rongtao
authors.initials: R
authors.lastname: Lai
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Discipline of Pathology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Shisan
authors.initials: S
authors.lastname: Bao
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000097:blood; D016022:Case-Control Studies; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000502:physiology*; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000201:enzymology*; D053244:Osteoprotegerin / Q000097:blood; D017207:Rats, Sprague-Dawley; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: C578813:A2M protein, human; D001057:Apolipoproteins E; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human; D000511:alpha-Macroglobulins; D003546:Cysteine Endopeptidases; C499718:SENP3 protein, human