C-C chemokine receptor 2 inhibitor ameliorates hepatic steatosis by improving ER stress and inflammation in a type 2 diabetic mouse model
- Abstract
- Hepatic steatosis is the accumulation of excess fat in the liver. Recently, hepatic steatosis has become more important because it occurs in the patients with obesity, type 2 diabetes, and hyperlipidemia and is associated with endoplasmic reticulum (ER) stress and insulin resistance. C-C chemokine receptor 2 (CCR2) inhibitor has been reported to improve inflammation and glucose intolerance in diabetes, but its mechanisms remained unknown in hepatic steatosis. We examined whether CCR2 inhibitor improves ER stress-induced hepatic steatosis in type 2 diabetic mice. In this study, db/db and db/m (n = 9) mice were fed CCR2 inhibitor (2 mg/kg/day) for 9 weeks. In diabetic mice, CCR2 inhibitor decreased plasma and hepatic triglycerides levels and improved insulin sensitivity. Moreover, CCR2 inhibitor treatment decreased ER stress markers (e.g., BiP, ATF4, CHOP, and XBP-1) and inflammatory cytokines (e.g., TNFα, IL-6, and MCP-1) while increasing markers of mitochondrial biogenesis (e.g., PGC-1α, Tfam, and COX1) in the liver. We suggest that CCR2 inhibitor may ameliorate hepatic steatosis by reducing ER stress and inflammation in type 2 diabetes mellitus.
- All Author(s)
- H. M. Kim
; E. S. Lee
; B. R. Lee
; D. Yadav
; Y. M. Kim
; H. J. Ko
; K. S. Park
; E. Y. Lee
; C. H. Chung
- Issued Date
- 2015
- Type
- Article
- Keyword
- Animals; Benzoxazines/*pharmacology; Blotting, Western; Cells, Cultured; Diabetes Mellitus, Experimental/*complications/physiopathology; Diabetes Mellitus, Type 2/*complications/physiopathology; Diet, High-Fat/adverse effects; Disease Models, Animal; *Endoplasmic Reticulum Stress; Fatty Liver/etiology/metabolism/*prevention & control; Glucose Tolerance Test; Humans; Immunoenzyme Techniques; Inflammation/etiology/metabolism/*prevention & control; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Obesity/complications; Piperidines/*pharmacology; RNA, Messenger/genetics; Real-Time Polymerase Chain Reaction; Receptors, CCR2/*antagonists & inhibitors; Reverse Transcriptase Polymerase Chain Reaction
- Publisher
- Public Library of Science
- ISSN
- 1932-6203
- Citation Title
- PLoS One
- Citation Volume
- 10
- Citation Number
- 3
- Citation Start Page
- e0120711
- Citation End Page
- e0120711
- Language(ISO)
- eng
- DOI
- 10.1371/journal.pone.0120711
- URI
- http://schca-ir.schmc.ac.kr/handle/2022.oak/1065
- 공개 및 라이선스
-
- 파일 목록
-
Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.