Fig. 5

Role of adiponectin signaling in the liver. Binding of adiponectin with AdipoR1 activates AMPK via APPL1/LKB1 or APPL1/PLC/Ca²⁺/CaMKK mediated signaling pathways. Activated AMPK subsequently inhibits the activities of PEPCK and G6Pase through the activation of EGR1 and DUSP4, which leads to decreased gluconeogenesis. Activated AMPK also decreases lipid biosynthesis through inhibiting sterol regulatory element-binding transcription factor 1c (SREBP1c)-mediated transcription of acetyl-CoA carboxylase (ACC), FAS and stearoyl-CoA desaturase (SCD)1. Additionally, activated AMPK increases abnormality in mitochondrial morphologies and fatty acid oxidation via sequestering the inhibitory effect of ACC-1 on carnitine palmitoyltransferase (CPT)-1 activation. Independent of AMPK activation, adiponectin also increases insulin sensitivity through the activation of AdipoR1 or AdipoR2 following CDase-mediated degradation of ceramides. Upon activation of AdipoR2 with the binding of adiponectin, fatty acid oxidation increases through PPARα-induced activation of acyl-CoA oxidase (ACO) and uncoupling protein (UCP)2. Adiponectin-induced activation of AdipoR1 contributes to the activation of antioxidant enzymes, superoxide dismutase (SOD)1 and catalase which subsequently decreases oxidative stress via downregulating ROS production. Adiponectin also protects hepatocytes through the inhibition of ROS-mediated activation of proinflammatory molecules including TNF-α and MCP1