CCR5 Plays a Critical Role in Obesity-induced Adipose Tissue Inflammation and Insulin Resistance by Regulating Both Macrophage Recruitment and M1/M2 Status

Overview

Journal Diabetes

Specialty Endocrinology

Date 2012 Apr 5

PMID 22474027

Citations 149

Authors

Hironori Kitade

Kazuki Sawamoto

Mayumi Nagashimada

Hiroshi Inoue

Yasuhiko Yamamoto

Yoshimichi Sai

Toshinari Takamura

Hiroshi Yamamoto

Ken-Ichi Miyamoto

Henry N Ginsberg

Naofumi Mukaida

Shuichi Kaneko

Tsuguhito Ota

Affiliations

Soon will be listed here.

Abstract

C-C motif chemokine receptor (CCR)2 and its ligand, monocyte chemoattractant protein (MCP)-1, are pivotal for adipose tissue macrophage (ATM) recruitment and the development of insulin resistance. However, other chemokine systems also may play a role in these processes. In this study, we investigated the role of CCR5 in obesity-induced adipose tissue inflammation and insulin resistance. We analyzed expression levels of CCR5 and its ligands in white adipose tissue (WAT) of genetically (ob/ob) and high-fat (HF) diet-induced obese (DIO) mice. Furthermore, we examined the metabolic phenotype of Ccr5(-/-) mice. CCR5 and its ligands were markedly upregulated in WAT of DIO and ob/ob mice. Fluorescence-activated cell sorter analysis also revealed that DIO mice had a robust increase in CCR5(+) cells within ATMs compared with chow-fed mice. Furthermore, Ccr5(-/-) mice were protected from insulin resistance, glucose intolerance, and hepatic steatosis induced by HF feeding. The effects of loss of CCR5 were related to both reduction of total ATM content and an M2-dominant shift in ATM polarization. It is noteworthy that transplantation of Ccr5(-/-) bone marrow was sufficient to protect against impaired glucose tolerance. CCR5 plays a critical role in ATM recruitment and polarization and subsequent development of insulin resistance.

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