Figure 2.

Dysfunctional intercellular signaling within macrophages, hepatocytes and adipocytes in the pathogenesis of obesity-related NAFLD. A_2AR, STING and Per1/2 are predominantly expressed in macrophages. Increased A_2AR and/or Per1/2 in macrophages functions to protect whereas up-activated cGAS-STING signaling pathway in macrophages functions to aggravate fat deposition and inflammatory responses in hepatocytes. Furthermore, overexpression of Per1/2 in macrophages inhibits inflammatory responses in adipocytes. MiR-155 from macrophages aggravates insulin resistance. In contrast, miR-34a from the adipocytes promotes the polarization of macrophages toward M2 cells from M1 cells. Moreover, stressed hepatocytes release increased numbers of EVs and promote macrophage activation and accumulation. ps: EVs: extracellular vesicles.