title: Menin liver-specific hemizygous mice challenged with high fat diet show increased weight gain and markers of metabolic impairment.
abstract: OBJECTIVE
  The menin tumor suppressor protein is abundantly expressed in the liver, although no function has been identified because of lack of tumor development in multiple endocrine neoplasia type 1 (Men1) null livers. We examine the phenotype of mice lacking one functional allele of Men1 (consistent with the phenotype in humans with MEN1 syndrome) challenged with high fat diet (HFD) to elucidate a metabolic function for hepatic menin.
  
  
  METHODS
  In this study, we challenged mice harboring a liver-specific hemizygous deletion of Men1 (HETs) alongside wild-type (WT) counterparts with HFD for 3 months and monitored the severity of metabolic changes. We demonstrate that the HET mice challenged with HFD for 3 months show an increased weight gain with decreased glucose tolerance compared with WT counterparts. Along with these changes, there was a more severe serum hormone profile involving increased serum insulin, glucose and glucagon, all hallmarks of the type 2 diabetic phenotype. In concert with increased serum hormones, we found that these mice have significantly increased liver triglycerides coupled with increased liver steatosis and inflammatory markers. Quantitative real-time PCR and western blotting studies show increases in enzymes involved with lipogenesis and hepatic glucose production.
  
  
  CONCLUSIONS
  We conclude that hepatic menin is required for regulation of diet-induced metabolism, and our studies indicate a protective role for the Men1 gene in the liver when challenged with HFD.
authors.affiliation: Department of Physiology and Pharmacology, Center for Diabetes and Endocrine Research, University of Toledo College of Medicine, Toledo, OH, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wuescher
authors.forename: K
authors.initials: K
authors.lastname: Angevine
authors.forename: P R
authors.initials: PR
authors.lastname: Patel
authors.forename: E
authors.initials: E
authors.lastname: Mensah-Osman