Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, Hangzhou, 310052, Zhejiang, China.
The First Affiliated Hospital, Anesthesiology, Zhejiang University School of Medicine, Hangzhou, China.
J Transl Med. 2019 Sep 2;17(1):300. doi: 10.1186/s12967-019-2050-9.
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 F4/80CD11c 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.
Trigger receptor expressed on myeloid cells 2 may function as a feedback mechanism to curb obesity-induced insulin resistance via regulating adipose tissue remodeling.
脂肪组织重塑在肥胖引起的胰岛素抵抗中起着重要作用。已发表的研究报告称，肥胖动物模型中脂肪组织中髓样细胞触发受体 2（TREM2）的水平上调。本研究旨在探讨 TREM2 是否通过调节高脂肪饮食（HFD）小鼠的脂肪组织重塑来调节肥胖引起的胰岛素抵抗。
野生型（WT）和 TREM2 小鼠均喂食控制脂肪饮食（CFD）或 HFD 12 周，并研究肥胖和胰岛素抵抗。同时，检查附睾脂肪组织（EAT）的形态和病理变化，以确定脂肪组织重塑。之后，测量脂肪细胞、脂肪组织和循环中的脂肪细胞衍生的单核细胞趋化蛋白 1（MCP-1）。接下来，测定脂肪组织巨噬细胞（ATM）中的炎性细胞因子。最后，分析肝脏的肝脂肪变性。
与 WT 相比，HFD 上的 TREM2 小鼠肥胖和胰岛素抵抗增加。TREM2 小鼠的脂肪组织质量减少，但脂肪细胞肥大和脂肪细胞死亡增加。此外，TREM2 小鼠的脂肪细胞衍生的 MCP-1 下调，循环 MCP-1 水平低于 WT 小鼠。此外，TREM2 小鼠表现出脂肪组织中 F4/80CD11c 巨噬细胞浸润减少，无法形成清除死脂肪细胞和细胞内容物的冠状结构（CLS）。此外，TREM2 缺乏增强了 HFD 小鼠脂肪组织巨噬细胞的炎症反应。此外，与 WT 相比，TREM2 小鼠在 HFD 喂养下表现出更严重的肝脂肪变性。
髓样细胞触发受体 2 可能作为一种反馈机制，通过调节脂肪组织重塑来抑制肥胖引起的胰岛素抵抗。
