C-C Chemokine Receptor 2 Inhibitor Ameliorates Hepatic Steatosis by Improving ER Stress and Inflammation in a Type 2 Diabetic Mouse Model
- Authors
- Kim, Hong-Min; Lee, Eun Soo; Lee, Bo Ra; Yadav, Dhananjay; Kim, You Mi; Ko, Hyun-Jeong; Park, Kyu Sang; Lee, Eun Young; Chung, Choon Hee
- Issue Date
- 27-Mar-2015
- Publisher
- Public Library of Science
- Keywords
- C-C Chemokine Receptor 2 Inhibitor Ameliorates Hepatic Steatosis by Improving ER Stress and Inflammation in a Type 2 Diabetic Mouse Model
- Citation
- PLoS ONE, v.10, no.3
- Journal Title
- PLoS ONE
- Volume
- 10
- Number
- 3
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/10783
- DOI
- 10.1371/journal.pone.0120711
- ISSN
- 1932-6203
- 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., TNF alpha, IL-6, and MCP-1) while increasing markers of mitochondrial biogenesis (e.g., PGC-1 alpha, 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.
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Collections - College of Medicine > Department of Internal Medicine > 1. Journal Articles
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