CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype
作者单位：Fourth Military Medical University Institute of Medical ResearchNorthwestern Polytechnical University
会议名称：《第十四届全国免疫学学术大会》
会议日期：2021年
关 键 词：CD226 HFD obesity macrophage polarization
摘 要：Macrophage M1 polarization plays a crucial role in promoting insulin resistance and fatty liver caused by obesity.However,the regulatory mechanism of adipose tissue macrophages(ATMs) has not yet been well described.Using a high-fat diet(HFD)-induced mouse obesity model,we found that the costimulatory molecule CD226 was highly expressed on ATMs and knockout(KO) of CD226 alleviated obesity and its related liver damage.Loss of CD226 reduced the proportion of macrophages in adipose tissue and lowered serum proinflammatory cytokine levels,which hindered macrophage M1 polarization.In CD226 KO mice fed with a high-fat diet,serum levels of IL-1,IL-12,and TNF-α and the chemokines CCL3 and CXCL16,which are associated with the fatty liver progression,were significantly lower than those in wildtype mice.Furthermore,deficiency of CD226 on macrophages decreased the phosphorylation levels of VAV,Akt,and Foxo1 and thereby upregulated PPARγ.Further administration of PPARγ inhibitor restored the inflammatory factor levels.In summary,loss of CD226 alleviates the HFD-induced obesity and liver damage through inhibition of the accumulation and M1 polarization of ATMs in which PPARγ-dependent signaling pathway is involved,suggesting that CD226 may be identified as a potential molecular target for the clinical treatment of obesity.