title: Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance.
abstract: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic insulin clearance. Liver-specific inactivation or global null-mutation of Ceacam1 impairs hepatic insulin extraction to cause chronic hyperinsulinemia, resulting in insulin resistance and visceral obesity. In this study we investigated whether diet-induced insulin resistance implicates changes in hepatic CEACAM1. We report that feeding C57/BL6J mice a high-fat diet reduced hepatic CEACAM1 levels by >50% beginning at 21 days, causing hyperinsulinemia, insulin resistance, and elevation in hepatic triacylglycerol content. Conversely, liver-specific inducible CEACAM1 expression prevented hyperinsulinemia and markedly limited insulin resistance and hepatic lipid accumulation that were induced by prolonged high-fat intake. This was partly mediated by increased hepatic β-fatty acid oxidation and energy expenditure. The data demonstrate that the high-fat diet reduced hepatic CEACAM1 expression and that overexpressing CEACAM1 in liver curtailed diet-induced metabolic abnormalities by protecting hepatic insulin clearance.
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH.
authors.forename: Qusai Y
authors.initials: QY
authors.lastname: Al-Share
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: DeAngelis
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH.
authors.forename: Sumona Ghosh
authors.initials: SG
authors.lastname: Lester
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bowman
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH.
authors.forename: Sadeesh K
authors.initials: SK
authors.lastname: Ramakrishnan
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH.
authors.forename: Simon L
authors.initials: SL
authors.lastname: Abdallah
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH.
authors.forename: Lucia
authors.initials: L
authors.lastname: Russo
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH.
authors.forename: Payal R
authors.initials: PR
authors.lastname: Patel
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH.
authors.forename: Meenakshi K
authors.initials: MK
authors.lastname: Kaw
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH.
authors.forename: Christian K
authors.initials: CK
authors.lastname: Raphael
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Rehabilitation Sciences, College of Health Sciences, The University of Toledo, Toledo, OH.
authors.forename: Andrea Jung
authors.initials: AJ
authors.lastname: Kim
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Rehabilitation Sciences, College of Health Sciences, The University of Toledo, Toledo, OH.
authors.forename: Garrett
authors.initials: G
authors.lastname: Heinrich
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Rehabilitation Sciences, College of Health Sciences, The University of Toledo, Toledo, OH.
authors.forename: Abraham D
authors.initials: AD
authors.lastname: Lee
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
authors.forename: Rohit N
authors.initials: RN
authors.lastname: Kulkarni
authors.affiliation: Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: William M
authors.initials: WM
authors.lastname: Philbrick
authors.affiliation: Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH sonia.najjar@utoledo.edu.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Najjar
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D006946:Hyperinsulinism / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D005227:Fatty Acids; D007328:Insulin