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


ABSTRACT: 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 C57BL/6J 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.

SUBMITTER: Zhang H 

PROVIDER: S-EPMC7280146 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Zhang Heng H   Li Qingjie Q   Teng Yuxin Y   Lin Yubi Y   Li Shaojian S   Qin Tingfeng T   Chen Linxi L   Huang Jiana J   Zhai Hening H   Yu Quan Q   Xu Geyang G  

Acta pharmaceutica Sinica. B 20200107 5


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 a  ...[more]

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