CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype.
CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype.
复制标题
CD226敲除通过抑制促炎巨噬细胞表型减轻高脂饮食引起的肥胖
DOI：
10.1186/s12967-021-03150-4
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发表时间：
2021-11-25
影响因子：
7.4
通讯作者：
Zhuang R
中科院分区：
文献类型：
--
作者：
Ma J;Hu W;Zhang D;Xie J;Duan C;Liu Y;Wang Y;Xu X;Cheng K;Jin B;Zhang Y;Zhuang R
Obesity is associated with chronic low-grade inflammation, contributing to an increasing prevalence of chronic metabolic diseases, such as insulin resistance, non-alcoholic fatty liver disease (NALFD), and steatohepatitis. Macrophages are the predominant immune cells in adipose tissues. Adipose tissue macrophages (ATMs) would switch to pro-inflammatory M1 state during obesity, causing local and systemic inflammation. However, the regulatory mechanism of ATMs has not yet been well described within this process. 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 caused by HFD. Loss of CD226 reduced the accumulation of ATMs and hindered macrophage M1 polarization, with lower serum proinflammatory cytokine levels. Furthermore, deficiency of CD226 on ATMs decreased the phosphorylation levels of VAV1, AKT, and FOXO1 and thereby upregulated PPAR-γ. Further administration of PPAR-γ inhibitor restored M1 phenotype in CD226KO ATMs. In summary, loss of CD226 alleviates the HFD-induced obesity and systemic inflammation through inhibition of the accumulation and M1 polarization of ATMs in which PPAR-γ-dependent signaling pathway is involved, suggesting that CD226 may be identified as a potential molecular target for the clinical treatment of obesity. The online version contains supplementary material available at 10.1186/s12967-021-03150-4.
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影响因子：
14.2
作者：
Lee, Kyung Sun;Kim, So Ri;Lee, Yong Chul
通讯作者：
Lee, Yong Chul
DOI：
10.1073/pnas.1814052115
发表时间：
2018-12-11
影响因子：
11.1
作者：
Du X;de Almeida P;Manieri N;de Almeida Nagata D;Wu TD;Harden Bowles K;Arumugam V;Schartner J;Cubas R;Mittman S;Javinal V;Anderson KR;Warming S;Grogan JL;Chiang EY
通讯作者：
Chiang EY
影响因子：
12.7
作者：
Baufeld C;Osterloh A;Prokop S;Miller KR;Heppner FL
通讯作者：
Heppner FL
影响因子：
6.1
作者：
Kim, Dae Hyun;Lee, Bonggi;Chung, Hae Young
通讯作者：
Chung, Hae Young
影响因子：
7.3
作者：
Gaud, Guillaume;Roncagalli, Romain;Saoudi, Abdelhadi
通讯作者：
Saoudi, Abdelhadi