title: Mst1 regulates hepatic lipid metabolism by inhibiting Sirt1 ubiquitination in mice.
abstract: Previous study showed mammalian Ste20-like kinase (Mst1) may serve as target for the development of new therapies for diabetes. However, the function of Mst1 involved in liver lipid metabolism has remained elusive. In this study, we report that the liver of Mst1 knockout (Mst1(-/-)) mice showed more severe liver metabolic damage under fasting and high-fat diet than that of control mice. And fasting induced hepatic Mst1 expression. Mst1 overexpression inhibited Srebp-1c expression and increased the expression of antioxidant genes in primary hepatocytes. We also found that fasting-induced expression of hepatic Sirt1 was attenuated in Mst1(-/-) mice. Mst1 overexpression promoted Sirt1 expression, probably due to inhibiting Sirt1 ubiquitination. In summary, our study suggests that Mst1 regulates hepatic lipid metabolism by inhibiting Sirt1 ubiquitination in mice.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, #5 Dongdansantiao, Beijing 100005, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Geng
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, #5 Dongdansantiao, Beijing 100005, China.
authors.forename: Yinliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, #5 Dongdansantiao, Beijing 100005, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Genetic Engineering and Institute of Developmental Biology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Wufan
authors.initials: W
authors.lastname: Tao
authors.affiliation: Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei 230032, China.
authors.forename: Huabing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, #5 Dongdansantiao, Beijing 100005, China. Electronic address: xiaojunliu@ibms.pumc.edu.cn.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, #5 Dongdansantiao, Beijing 100005, China. Electronic address: fangfd@vip.sina.com.
authors.forename: Fude
authors.initials: F
authors.lastname: Fang
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, #5 Dongdansantiao, Beijing 100005, China. Electronic address: changy@ibms.pumc.edu.cn.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005215:Fasting; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000099317:Hippo Kinases
chemical_list: D000975:Antioxidants; D017346:Protein Serine-Threonine Kinases; D056564:Sirtuin 1; C490660:Stk4 protein, mouse; D000099317:Hippo Kinases; C470545:Sirt1 protein, mouse
keywords: Mst1; Non-alcoholic fatty liver disease; Oxidant stress; Sirt1