Signalling transduction via adiponectin receptors (AdipoR1 and AdipoR2) activation. The binding of the different forms of adiponectin to the two known adiponectin receptors, AdipoR1 and AdipoR2, can lead to stimulation of various signaling pathways. Indeed, interacting directly with the N-terminal of at least AdipoR1 and possibly AdipoR2, APPL1 elicits signalling through not only PPARα, AMPK, and AMPK/SIRT1 but also p38-MAPK, ERK1/2-MAPK, and Akt. APPL2 binds to AdipoR1 and AdipoR2. Unlike APPL1, APPL2 inhibits AdipoR1 dependent signaling. According to the tissue, activation of both receptors results in modulation of different biological effects such as steroidogenesis, glucose uptake, cell survival, fatty acid oxidation, vasodilatation, and cytoprotection. APPL1/2: adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif 1; PPARα: peroxisome proliferator-activated receptor α; SIRT1: sirtuin 1 (a NAD-dependent deacetylase); AMPK: 5′ adenosine monophosphate-activated protein kinase; MAPK: Mitogen-activated protein kinase; ERK1/2: extracellular signal-regulated kinases 1/2 (−: inhibition).
