C-C chemokine receptor 2 inhibitor ameliorates hepatic steatosis by improving er stress and inflammation in a type 2 diabetic mouse model

Hong Min Kim, Eun Soo Lee, Bo Ra Lee, Dhananjay Yadav, You Mi Kim, Hyun Jeong Ko, Kyusang Park, Eun Young Lee, Choon Hee Chung

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Article numbere0120711
JournalPLoS One
Volume10
Issue number3
DOIs
Publication statusPublished - 2015 Mar 27

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CC Chemokines
Chemokine Receptors
fatty liver
inflammation
animal models
Inflammation
endoplasmic reticulum
Endoplasmic Reticulum Stress
Liver
Medical problems
noninsulin-dependent diabetes mellitus
insulin resistance
liver
mice
Insulin
Type 2 Diabetes Mellitus
Insulin Resistance
1-methylcyclopropene
hyperlipidemia
interleukin-6

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kim, Hong Min ; Lee, Eun Soo ; Lee, Bo Ra ; Yadav, Dhananjay ; Kim, You Mi ; Ko, Hyun Jeong ; Park, Kyusang ; Lee, Eun Young ; Chung, Choon Hee. / C-C chemokine receptor 2 inhibitor ameliorates hepatic steatosis by improving er stress and inflammation in a type 2 diabetic mouse model. In: PLoS One. 2015 ; Vol. 10, No. 3.
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C-C chemokine receptor 2 inhibitor ameliorates hepatic steatosis by improving er stress and inflammation in a type 2 diabetic mouse model. / Kim, Hong Min; Lee, Eun Soo; Lee, Bo Ra; Yadav, Dhananjay; Kim, You Mi; Ko, Hyun Jeong; Park, Kyusang; Lee, Eun Young; Chung, Choon Hee.

In: PLoS One, Vol. 10, No. 3, e0120711, 27.03.2015.

Research output: Contribution to journalArticle

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AU - Kim, You Mi

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AU - Park, Kyusang

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