title: Role for hepatic CEACAM1 in regulating fatty acid metabolism along the adipocyte-hepatocyte axis.
abstract: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic insulin clearance and mediating suppression of fatty acid synthase activity. Feeding C57BL/6J male mice with a high-fat (HF) diet for 3-4 weeks triggered a >60% decrease in hepatic CEACAM1 levels to subsequently impair insulin clearance and cause systemic insulin resistance and hepatic steatosis. This study aimed at investigating whether lipolysis drives reduction in hepatic CEACAM1 and whether this constitutes a key mechanism leading to diet-induced metabolic abnormalities. Blocking lipolysis with a daily intraperitoneal injection of nicotinic acid in the last two days of a 30-day HF feeding regimen demonstrated that white adipose tissue (WAT)-derived fatty acids repressed hepatic CEACAM1-dependent regulation of insulin and lipid metabolism in 3-month-old male C57BL/6J mice. Adenoviral-mediated CEACAM1 redelivery countered the adverse metabolic effect of the HF diet on insulin resistance, hepatic steatosis, visceral obesity, and energy expenditure. It also reversed the effect of HF diet on inflammation and fibrosis in WAT and liver. This assigns a causative role for lipolysis-driven decrease in hepatic CEACAM1 level and its regulation of insulin and lipid metabolism in sustaining systemic insulin resistance, hepatic steatosis, and other abnormalities associated with excessive energy supply.
authors: Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614.
authors: Lucia
authors: L
authors: Russo
authors: Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614.
authors: Hilda E
authors: HE
authors: Ghadieh
authors: Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614.
authors: Simona S
authors: SS
authors: Ghanem
authors: Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614.
authors: Qusai Y
authors: QY
authors: Al-Share
authors: Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614.
authors: Zachary N
authors: ZN
authors: Smiley
authors: Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614; Department of Pathology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614.
authors: Cara
authors: C
authors: Gatto-Weis
authors: Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614; Department of Medicinal and Biological Chemistry at the College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614.
authors: Emily L
authors: EL
authors: Esakov
authors: Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614; Department of Medicinal and Biological Chemistry at the College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614.
authors: Marcia F
authors: MF
authors: McInerney
authors: Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701.
authors: Garrett
authors: G
authors: Heinrich
authors: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48019.
authors: Xin
authors: X
authors: Tong
authors: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48019.
authors: Lei
authors: L
authors: Yin
authors: Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701. Electronic address: najjar@ohio.edu.
authors: Sonia M
authors: SM
authors: Najjar
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000502:physiology*; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005355:Fibrosis; D022781:Hepatocytes / Q000378:metabolism*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009525:Niacin / Q000494:pharmacology; D009765:Obesity / Q000209:etiology / Q000378:metabolism
chemical_list: D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D005227:Fatty Acids; D009525:Niacin
keywords: carcinoembryonic antigen-related cell adhesion molecule 1; insulin clearance; insulin resistance; lipolysis; nicotinic acid