Role for hepatic CEACAM1 in regulating fatty acid metabolism along the adipocyte-hepatocyte axis.

Autor:	Russo L; Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614., Ghadieh HE; Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614., Ghanem SS; Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614., Al-Share QY; Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614., Smiley ZN; Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH 43614., Gatto-Weis C; 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., Esakov EL; 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., McInerney MF; 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., Heinrich G; 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., Tong X; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48019., Yin L; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48019., Najjar SM; 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.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2016 Dec; Vol. 57 (12), pp. 2163-2175. Date of Electronic Publication: 2016 Oct 24.
DOI:	10.1194/jlr.M072066
Abstrakt:	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. (Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu