Figure 5.

A cross-talk between inflammatory pathways and RNA silencing machinery in hepatocytes in the pathogenesis of obesity. Biological interaction between inflammatory signaling pathway and protein translation regulation via PKR within the hepatocyte in metabolic stress responses. PKR is activated by lipid-mediated stress within obese metabolic tissues and induces concordant inflammatory responses, in which endogenous dsRNAs mediate PKR activation. Upon activation, PKR forms an inflammatory protein complex, using TRBP, Dicer, and RNA-induced silencing complex (RISC), which leads to protein translation suppression via phosphorylation of elf2α and enhances inflammation via activation of JNK pathway. Ago2-mediated RNA silencing that regulates protein translation also plays a critical role in disputing metabolic homeostasis in the pathogenesis of obesity.