Figure 4.

The role of IL-6 deficiency in the AMPK/ACC axis. IL-6 deficiency inhibits FA oxidation and mitochondria biogenesis through multistep pathways, thereby resulting in cardiac ATP depletion. Consequently, reduced [AMP]/[ATP] ratio activates AMPK and subsequently stimulates ACC which in turn catalyzes the conversion of acetyl CoA to malonyl CoA. As this reaction is the rate-limiting step in FA de novo synthesis, activation of ACC promotes TG pool expansion and lipotoxicity. Moreover, malonyl CoA inhibits CPT1 which is responsible for translocation of activated FA into mitochondria for oxidation, thereby exacerbating lipid accumulation and lipotoxicity. Black arrows denote stimulatory or consequential effects of upstream factors and red arrows indicate inhibitory effects. FA, fatty acid; CPT1, carnitine palmitoyltransferase-1 (CPT-1); AMPK, AMP-activated protein kinase; ACC, acetyl-CoA carboxylase; TG, triglycerides.