TREM2 Regulates Obesity-induced Insulin Resistance Via Adipose Tissue Remodeling in Mice of High-fat Feeding

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2019 Sep 4

PMID 31477129

Citations 27

Authors

Can Liu

Pinhao Li

Hui Li

Sicong Wang

Lifeng Ding

Hanbin Wang

Hui Ye

Yue Jin

Jinchao Hou

Xiangming Fang

Qiang Shu

Affiliations

Soon will be listed here.

Abstract

Background: Adipose tissue remodeling plays a significant role in obesity-induced insulin resistance. Published studies reported that level of trigger receptor expressed on myeloid cells 2 (TREM2) in adipose tissue is up-regulated in animal models of obesity. This study aims to investigate whether TREM2 regulates obesity-induced insulin resistance via modulating adipose tissue remodeling in mice of high-fat diet (HFD).

Methods: Wild-type (WT) and TREM2 mice were both fed with a controlled-fat diet (CFD) or HFD for 12 weeks and studied for obesity and insulin resistance. Meanwhile, epididymal adipose tissue (EAT) was examined for morphological and pathological changes to determine adipose tissue remodeling. After that, adipocyte-derived MCP-1 was measured in adipocytes, adipose tissue and circulation. Next, inflammatory cytokines were determined in adipose tissue macrophages (ATM). At last, livers were analyzed for hepatic steatosis.

Results: TREM2 mice on HFD had increased obesity and insulin resistance compared with WT counterparts. Adipose tissue from TREM2 mice exhibited reduced mass but greater adipocyte hypertrophy and increased adipocyte death. Besides, adipocyte-derived MCP-1 was down-regulated in TREM2 mice, and circulating MCP-1 level was lower than that of WT mice. Furthermore, TREM2 mice displayed reduced infiltration of F4/80CD11c macrophages into adipose tissue, which was unable to form crown-like structures (CLS) to clean dead adipocytes and cellular contents. Also, TREM2 deficiency augmented inflammatory response of adipose tissue macrophages in HFD mice. In addition, TREM2 mice demonstrated more severe hepatic steatosis than WT counterparts under HFD feeding.

Conclusions: Trigger receptor expressed on myeloid cells 2 may function as a feedback mechanism to curb obesity-induced insulin resistance via regulating adipose tissue remodeling.

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