1. Leptin and insulin signalling pathways in the Arc.
Leptin and insulin signalling pathways in the Arc. Signal transducer and activator of transcription 3 (STAT3) is activated and phosphorylated when leptin binds to LepR‐b. p‐STAT3 binds to pomc and agrp promoters, stimulating pomc expression and inhibiting agrp. Leptin and insulin signalling pathways converge on PI3K. Activation of PI3K leads to phosphorylation and inactivation of FoxO1, a repressor of pomc expression. Phosporylation of FoxO1 provokes its nuclear export and allows STAT3 to bind to pomc and agrp promoters. It has been reported that inhibition of AMPK by leptin is mediated by mTOR [[35]]. AgRP, agouti‐related protein; AKT, protein kinase B; AMPK, AMP‐dependent kinase; FoxO1, Forkhead box protein O1; HIF, hypoxia‐inducible factor; InsR, insulin receptor; IRS, insulin receptor substrate; JAK, Janus kinase; LepR‐b, leptin receptor b; mTOR, mammalian target of rapamycin; PDK1, 3‐phosphoinositide‐dependent protein kinase 1; PI3K, phosphatidylinositol‐3‐kinase; POMC, proopiomelanocortin,; S6K,; STAT3, signal transducer and activator of transcription 3.
Luis Varela, and Tamas L Horvath EMBO Rep. 2012;13:
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