文章基本信息

标题：CYP2J2 and Its Metabolites EETs Attenuate Insulin Resistance via Regulating Macrophage Polarization in Adipose Tissue
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作者：Meiyan Dai ; Lujin Wu ; Peihua Wang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/srep46743
语种：English
出版社：Springer Nature
摘要：Macrophages in adipose tissue are associated with obesity-induced low-grade inflammation, which contributed to insulin resistance and the related metabolic diseases. Previous studies demonstrated the beneficial effects of epoxyeicosatrienoic acids (EETs) on metabolic disorders and inflammation. Here we investigated the effects of CYP2J2-EETs-sEH metabolic pathway on insulin resistance in mice and the potential mechanisms. High fat diet (HFD)-induced obesity caused metabolic dysfunction with more weight gain, elevated glucose and lipids levels, impaired glucose tolerance and insulin sensitivity, while increase in EETs level by rAAV-mediated CYP2J2 overexpression, administration of sEH inhibit TUPS or EETs infusion significantly attenuated these metabolic disorders. EETs inhibited macrophages recruitment to adipose tissue and their switch to classically activated macrophage (M1) phenotype, while preserved the alternatively activated macrophage (M2) phenotype, which was accompanied by substantially reduced adipose tissue and systemic inflammation and insulin resistance. In vitro studies further clarified the effects of EETs on macrophage infiltration and polarization, and microarray assays showed that cAMP-EPAC signaling pathway was involved in these processes. Collectively, these results described key beneficial immune-regulatory properties and metabolic regulation of CYP2J2-EETs-sEH metabolic pathway, and indicated therapeutic potential of EETs in obesity-induced insulin resistance and related inflammatory diseases through modulating macrophage polarization targeting cAMP-EPAC signaling pathway.