title: Hepatic menin recruits SIRT1 to control liver steatosis through histone deacetylation.
abstract: OBJECTIVE
  The development and progression of non-alcoholic fatty liver disease are associated with aging, obesity, and type 2 diabetes. Understanding the precise regulatory networks of this process will contribute to novel therapeutic strategies.
  
  
  METHODS
  Hepatocyte-specific Men1 knockout mice were generated using Cre/loxP technology. Lipid and glucose metabolic phenotypes and mechanisms were investigated in aging and high-fat diet fed mice.
  
  
  RESULTS
  The expression of menin, encoded by multiple endocrine neoplasia 1 (Men1) gene, is reduced in the liver of aging mice. Hepatocyte-specific deletion of Men1 induces liver steatosis in aging mice. Menin deficiency promotes high-fat diet-induced liver steatosis in mice. Menin recruits SIRT1 to control hepatic CD36 expression and triglyceride accumulation through histone deacetylation.
  
  
  CONCLUSIONS
  Our work reveals that the adaptor protein menin is critical for the progression of hepatic steatosis during aging and metabolic imbalance.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases and Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Cao
authors.forename: Ying
authors.initials: Y
authors.lastname: Xue
authors.forename: Lu
authors.initials: L
authors.lastname: Xue
authors.forename: Xiuli
authors.initials: X
authors.lastname: Jiang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Jieli
authors.initials: J
authors.lastname: Lu
authors.forename: Changxian
authors.initials: C
authors.lastname: Zhang
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000107:Acetylation; D000375:Aging / Q000378:metabolism*; D000818:Animals; D018955:CD36 Antigens / Q000502:physiology; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D056564:Sirtuin 1 / Q000502:physiology*
chemical_list: D018955:CD36 Antigens; D006657:Histones; C484898:Men1 protein, mouse; D011518:Proto-Oncogene Proteins; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D005947:Glucose
keywords: Aging; HFD; Histone deacetylation; IPGTT; ITT; LMKO; Liver steatosis; MEN1; Menin; NAFLD; SIRT1; Scd-1; TC; TG; high-fat diet; insulin tolerance tests; intra-peritoneal glucose tolerance tests; liver-specific Men1 knockout mice; multiple endocrine neoplasia type 1; non-alcoholic fatty liver disease; stearoyl CoA desaturase-1; total cholesterol; triglyceride