title: High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion.
abstract: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis.
authors.affiliation: Division of Endocrinology and Metabolism, University of Virginia Health System, Charlottesville, Virginia; and.
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Endocrinology and Metabolism, University of Virginia Health System, Charlottesville, Virginia; and.
authors.forename: Silas A
authors.initials: SA
authors.lastname: Culver
authors.affiliation: Division of Endocrinology and Metabolism, University of Virginia Health System, Charlottesville, Virginia; and.
authors.forename: Syed
authors.initials: S
authors.lastname: Quadri
authors.affiliation: Center for Diabetes and Endocrinology Research, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Ledford
authors.affiliation: Center for Diabetes and Endocrinology Research, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio.
authors.forename: Qusai Y
authors.initials: QY
authors.lastname: Al-Share
authors.affiliation: Center for Diabetes and Endocrinology Research, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio.
authors.forename: Hilda E
authors.initials: HE
authors.lastname: Ghadieh
authors.affiliation: Center for Diabetes and Endocrinology Research, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Najjar
authors.affiliation: Division of Endocrinology and Metabolism, University of Virginia Health System, Charlottesville, Virginia; and hms7a@virginia.edu.
authors.forename: Helmy M
authors.initials: HM
authors.lastname: Siragy
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology; D018450:Disease Progression; D017353:Gene Deletion; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D004041:Dietary Fats
keywords: carcinoembryonic antigen-related cell adhesion molecule 1; high-fat diet; kidney; phosphatidylinositol 3′-kinase; renin-angiotensin system