Figure 7

Schematic representation showing that intracellular lipid droplet accumulation affects Jak-Stat signaling by two possible mechanisms. (i) Intracellular fat accumulation induces the ER stress related proteins ATF-6, BIP, IRE1-α, and this causes phophorylation of eIF2 α which leads to the down regulation of IFNAR1 expression. The reduced expression of IFNAR1 affects IFN-α binding, Jak-Stat signaling, and downstream antiviral responses. IFN-α binds to its cell surface receptor that activates Jak1 and Tyk2 phosphorylation. The activation of Jak1 and Tyk2 is required for the Stat1 and Stat2 phosphorylation. pStat1 and pStat2 bind to IRF9 to form a complex that translocates to the nucleus to induce IFN-stimulated gene expression. (ii) We show here that FFA treatment induces SOCS3 that also inhibits the phosphorylation of Stat1 and Stat2.