TREM2 regulates obesity-induced insulin resistance via adipose tissue remodeling in mice of high-fat feeding

作者：Can Liu, Pinhao Li, Hui Li, Sicong Wang, Lifeng Ding, Hanbin Wang, Hui Ye, Yue Jin, Jinchao Hou, Xiangming Fang, Qiang Shu · 发表于：Journal of Translational Medicine · 年份：2019 · DOI：10.1186/s12967-019-2050-9 · 被引用次数：68 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Inflammation biomarkers and pathways、Adipokines, Inflammation, and Metabolic Diseases

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). 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. 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 F4/80 + CD11c + macrophages into adipose tissue, which was unable to form crown-like structures (CLS) to clean dead adipocytes and cellular contents. Also, ...