CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status.
CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status.
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作者：
Kitade H;Sawamoto K;Nagashimada M;Inoue H;Yamamoto Y;Sai Y;Takamura T;Yamamoto H;Miyamoto K;Ginsberg HN;Mukaida N;Kaneko S;Ota T
C-C基序趋化因子受体(CCR)2及其配体单核细胞趋化蛋白(MCP)-1在脂肪组织巨噬细胞(ATM)募集和胰岛素抵抗的发生发展中起关键作用。然而，其他趋化因子系统也可能在这些过程中发挥作用。在这项研究中，我们研究了CCR5在肥胖引起的脂肪组织炎症和胰岛素抵抗中的作用。我们分析了CCR5及其配体在遗传性(ob/ob)和高脂(HF)饮食诱导的肥胖(DIO)小鼠白色脂肪组织(WAT)中的表达水平。此外，我们还检测了CCR5−/−小鼠的代谢表型。CCR5及其配体在DIO和ob/ob小鼠的WAT中显著上调。荧光激活的细胞分类分析还显示，与喂食食物的小鼠相比，DIO小鼠ATM中CCR5+细胞的数量有显著增加。此外，CCR5−/−小鼠还可以预防由HF喂养引起的胰岛素抵抗、糖耐量异常和肝脏脂肪变性。CCR5缺失的影响既与ATM总量的减少有关，也与ATM极化中M2主导的转移有关。值得注意的是，移植CCR5−/−骨髓足以保护糖耐量受损。CCR5在ATM的募集和极化以及随后的胰岛素抵抗的发展中起着关键作用。
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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