title: Suv39h2 deficiency ameliorates diet-induced steatosis in mice.
abstract: Steatosis is a prototypical metabolic disorder characterized by accumulation of lipid droplets in the liver, extensive hepatic inflammation, and, in advanced stages, accelerated liver fibrogenesis. The molecular mechanism underlying steatosis is not completely understood. In the present study we investigated the involvement of the histone methyltransferase Suv39h2 in the pathogenesis of steatosis. Expression of Suv39h2 was up-regulated in the liver in two different mouse models of steatosis. Suv39h2 knockout (KO) mice developed a less severe form of steatosis fed on a methione-and-choline deficient (MCD) diet, compared to wild type (WT) littermates, as evidenced by reduced levels of plasma ALT, down-regulated expression of pro-inflammatory mediators, and decreased infiltration of macrophages. In addition, Masson's trichrome staining as well as qPCR measurements of fibrogenic genes suggested that liver fibrosis was attenuated in MCD diet-fed KO mice compared to WT mice. Further analysis found that Suv39h2 repressed SIRT1 expression in the liver by stimulating histone H3K9 trimethylation surrounding the SIRT1 promoter and that Suv39h2 deficiency alleviated SIRT1 expression in MCD diet-fed mice. Therefore, our data support a role of Suv39h2 in promoting steatosis in mice likely through contributing to SIRT1 trans-reperssion.
authors.affiliation: College of Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.
authors.forename: Luyang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Xu
authors.affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.affiliation: School of Nursing, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Bian
authors.affiliation: Department of Nursing, Jiangsu Jiankang Vocational College, Nanjing, China. Electronic address: dafeifang@163.com.
authors.forename: Mingming
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China. Electronic address: yjxu@njmu.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002796:Choline Deficiency; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D015870:Gene Expression; D011495:Histone-Lysine N-Methyltransferase / Q000172:deficiency / Q000235:genetics*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism; D008715:Methionine / Q000172:deficiency; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D008715:Methionine; D011495:Histone-Lysine N-Methyltransferase; C000592056:Suv39h2 protein, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: Epigenetics; SIRT1; Steatosis; Suv39h2