Interleukin-27 decreases ghrelin production through signal transducer and activator of transcription 3—mechanistic target of rapamycin signaling

Interleukin-27(IL-27),a heterodimeric cytokine,plays a protective role in diabetes.Ghrelin,a gastric hormone,provides a hunger signal to the central nervous system to stimulate food intake.The relationship between IL-27 and ghrelin is still unexplored.Here we investigated that signal transducer and activator of transcription 3(STAT3)—mechanistic target of rapamycin(mTOR)signaling mediates the suppression of ghrelin induced by IL-27.Co-localization of interleukin 27 receptor subunit alpha(WSX-1)and ghrelin was observed in mouse and human gastric mucosa.Intracerebroventricular injection of IL-27 markedly suppressed ghrelin synthesis and secretion while stimulating STAT3-mTOR signaling in both C57 BL/6 J mice and high-fat diet-induced-obese mice.IL-27 inhibited the production of ghrelin in mHypoE-N42 cells.Inhibition of mTOR activity induced by mTOR siRNA or rapamycin blocked the suppression of ghrelin production induced by IL-27 in mHypoE-N42 cells.Stat 3 siRNA also abolished the inhibitory effect of IL-27 on ghrelin.IL-27 increased the interaction between STAT3 and mTOR in mHypoE-N42 cells.In conclusion,IL-27 suppresses ghrelin production through the STAT3-mTOR dependent mechanism.