title: Reduced Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Obesity.
abstract: Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease. Thus, we aimed to determine whether this occurs at the hepatocyte level in response to systemic extrahepatic factors and whether this holds across species. Northern and Western blot analyses demonstrate thatCEACAM1mRNA and protein levels are reduced in liver tissues of obese individuals compared to their lean age-matched counterparts. Furthermore, Western analysis reveals a comparable reduction of CEACAM1 protein in primary hepatocytes derived from the same obese subjects. Similar to humans,Ceacam1mRNA level, assessed by quantitative RT-PCR analysis, is significantly reduced in the livers of obese Zucker (fa/fa, ZDF) and Koletsky (f/f) rats relative to their age-matched lean counterparts. These studies demonstrate that the reduction of hepatic CEACAM1 in obesity occurs at the level of hepatocytes and identify the reduction of hepatic CEACAM1 as a common denominator of obesity across multiple species.
authors.affiliation: Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA; Diabetes Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA.
authors.forename: Garrett
authors.initials: G
authors.lastname: Heinrich
authors.affiliation: Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University , Athens, OH , USA.
authors.forename: Harrison T
authors.initials: HT
authors.lastname: Muturi
authors.affiliation: Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo , Toledo, OH , USA.
authors.forename: Khadijeh
authors.initials: K
authors.lastname: Rezaei
authors.affiliation: Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo , Toledo, OH , USA.
authors.forename: Qusai Y
authors.initials: QY
authors.lastname: Al-Share
authors.affiliation: Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo , Toledo, OH , USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: DeAngelis
authors.affiliation: Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo , Toledo, OH , USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bowman
authors.affiliation: Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo , Toledo, OH , USA.
authors.forename: Hilda E
authors.initials: HE
authors.lastname: Ghadieh
authors.affiliation: Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo , Toledo, OH , USA.
authors.forename: Simona S
authors.initials: SS
authors.lastname: Ghanem
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School , Ann Arbor, MI , USA.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Yale Cancer Center, Office of Research Affairs , New Haven, CT , USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Garofalo
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School , Ann Arbor, MI , USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA; Diabetes Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA; Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo, Toledo, OH, USA.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Najjar
keywords: carcinoembryonic antigen-related cell adhesion molecule 1; fatty liver disease; hyperinsulinemia; insulin clearance; insulin resistance; obesity