Deletion of Macrophage Vitamin D Receptor Promotes Insulin Resistance and Monocyte Cholesterol Transport to Accelerate Atherosclerosis in Mice
| Autor: | Jisu Oh, Jian Su Shao, Richard E. Ostlund, Kathleen Chin, Geert Carmeliet, Carlos Bernal-Mizrachi, Katsuhiko Funai, Oscar L. Sierra, Isra Darwech, Amy E. Riek |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty MAP Kinase Kinase 4 CD36 030209 endocrinology & metabolism Biology Calcitriol receptor Monocytes Article General Biochemistry Genetics and Molecular Biology Sarcoplasmic Reticulum Calcium-Transporting ATPases Mice 03 medical and health sciences 0302 clinical medicine Insulin resistance Internal medicine polycyclic compounds medicine Animals Macrophage Scavenger receptor lcsh:QH301-705.5 Bone Marrow Transplantation 030304 developmental biology Foam cell Receptors Scavenger 0303 health sciences Macrophages digestive oral and skin physiology Biological Transport Atherosclerosis Endoplasmic Reticulum Stress M2 Macrophage medicine.disease Mice Inbred C57BL PPAR gamma Cholesterol Endocrinology Liver lcsh:Biology (General) biology.protein Receptors Calcitriol Cytokine secretion lipids (amino acids peptides and proteins) Insulin Resistance Calcium-Calmodulin-Dependent Protein Kinase Type 2 Gene Deletion Foam Cells |
| Zdroj: | Cell Reports, Vol 10, Iss 11, Pp 1872-1886 (2015) |
| ISSN: | 2211-1247 |
| Popis: | Intense effort has been devoted to understanding predisposition to chronic systemic inflammation because it contributes to cardiometabolic disease. We demonstrate that deletion of the macrophage vitamin D receptor (VDR) in mice (KODMAC) is sufficient to induce insulin resistance by promoting M2 macrophage accumulation in the liver as well as increasing cytokine secretion and hepatic glucose production. Moreover, VDR deletion increases atherosclerosis by enabling lipid-laden M2 monocytes to adhere, migrate, and carry cholesterol into the atherosclerotic plaque and by increasing macrophage cholesterol uptake and esterification. Increased foam cell formation results from lack of VDR-SERCA2b interaction, causing SERCA dysfunction, activation of ER stress-CaMKII-JNKp-PPARγ signaling, and induction of the scavenger receptors CD36 and SR-A1. Bone marrow transplant of VDR-expressing cells into KODMAC mice improved insulin sensitivity, suppressed atherosclerosis, and decreased foam cell formation. The immunomodulatory effects of vitamin D in macrophages are thus critical in diet-induced insulin resistance and atherosclerosis in mice. publisher: Elsevier articletitle: Deletion of Macrophage Vitamin D Receptor Promotes Insulin Resistance and Monocyte Cholesterol Transport to Accelerate Atherosclerosis in Mice journaltitle: Cell Reports articlelink: http://dx.doi.org/10.1016/j.celrep.2015.02.043 content_type: article copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. ispartof: Cell Reports vol:10 issue:11 pages:1872-86 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|