title: PPARα (Peroxisome Proliferator-activated Receptor α) Activation Reduces Hepatic CEACAM1 Protein Expression to Regulate Fatty Acid Oxidation during Fasting-refeeding Transition.
abstract: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed at high levels in the hepatocyte, consistent with its role in promoting insulin clearance in liver. CEACAM1 also mediates a negative acute effect of insulin on fatty acid synthase activity. Western blot analysis reveals lower hepatic CEACAM1 expression during fasting. Treating of rat hepatoma FAO cells with Wy14,643, an agonist of peroxisome proliferator-activated receptor α (PPARα), rapidly reduces Ceacam1 mRNA and CEACAM1 protein levels within 1 and 2 h, respectively. Luciferase reporter assay shows a decrease in the promoter activity of both rat and mouse genes by Pparα activation, and 5'-deletion and block substitution analyses reveal that the Pparα response element between nucleotides -557 and -543 is required for regulation of the mouse promoter activity. Chromatin immunoprecipitation analysis demonstrates binding of liganded Pparα toCeacam1promoter in liver lysates ofPparα(+/+), but notPparα(-/-)mice fed a Wy14,643-supplemented chow diet. Consequently, Wy14,643 feeding reduces hepatic Ceacam1 mRNA and CEACAM1 protein levels, thus decreasing insulin clearance to compensate for compromised insulin secretion and maintain glucose homeostasis and insulin sensitivity in wild-type mice. Together, the data show that the low hepatic CEACAM1 expression at fasting is mediated by Pparα-dependent mechanisms. Changes in CEACAM1 expression contribute to the coordination of fatty acid oxidation and insulin action in the fasting-refeeding transition.
authors: From the Center for Diabetes and Endocrine Research and Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
authors: Sadeesh K
authors: SK
authors: Ramakrishnan
authors: From the Center for Diabetes and Endocrine Research and Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
authors: Saja S
authors: SS
authors: Khuder
authors: From the Center for Diabetes and Endocrine Research and Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
authors: Qusai Y
authors: QY
authors: Al-Share
authors: From the Center for Diabetes and Endocrine Research and Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
authors: Lucia
authors: L
authors: Russo
authors: From the Center for Diabetes and Endocrine Research and Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
authors: Simon L
authors: SL
authors: Abdallah
authors: From the Center for Diabetes and Endocrine Research and Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
authors: Payal R
authors: PR
authors: Patel
authors: From the Center for Diabetes and Endocrine Research and Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
authors: Garrett
authors: G
authors: Heinrich
authors: From the Center for Diabetes and Endocrine Research and Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
authors: Harrison T
authors: HT
authors: Muturi
authors: Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
authors: Brahma R
authors: BR
authors: Mopidevi
authors: From the Center for Diabetes and Endocrine Research and Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
authors: Ana Maria
authors: AM
authors: Oyarce
authors: Departments of Internal Medicine, Division of Gastroenterology and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, and.
authors: Yatrik M
authors: YM
authors: Shah
authors: From the Center for Diabetes and Endocrine Research and Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
authors: Edwin R
authors: ER
authors: Sanchez
authors: From the Center for Diabetes and Endocrine Research and Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614, Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701 sonia.najjar@utoledo.edu.
authors: Sonia M
authors: SM
authors: Najjar
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D005227:Fatty Acids; D007328:Insulin; D047493:PPAR alpha; D012333:RNA, Messenger
keywords: CEACAM1; PPAR response element; fatty acid metabolism; fatty acid synthase (FAS); gene expression; insulin clearance; insulin secretion; peroxisome proliferator-activated receptor (PPAR)