Signal transduction of leptin receptor. Leptin signaling is based on the autophosphorylation of the leptin receptor, triggering the JAK2-STAT3, IRS/PI3K, MAPK-ERK, and AMPK pathways. JAK, Janus kinase; IRS, insulin receptor substrate; PI3K, phosphatidylinositol 3-kinase; PDE, phosphodiesterase; Akt, protein kinase B; SHP2, tyrosine-protein phosphatase 2 containing SH2; Grb2, growth factor receptor-bound protein 2; MAPK, mitogen-activated protein kinase; PTP, tyrosine-protein phosphatase; STAT, signal transducer and activator of transcription; ERK, extracellular signal-regulated kinase; SOCS3, cytokine signaling 3 suppressor; AMPK, 5′-adenosine monophosphate-activated protein kinase.