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

作　　者：Heng Zhang Qingjie Li Yuxin Teng Yubi Lin Shaojian Li Tingfeng Qin Linxi Chen Jiana Huang Hening Zhai Quan Yu Geyang Xu 

机构地区：[1]Department of Physiology,School of Medicine,Jinan University,Guangzhou 510632,China [2]Department of Cardiology and Cardiovascular Intervention,Interventional Medical Center,the Fifth Affiliated Hospital of Sun Yat-sen University,Zhuhai 519000,China [3]Endoscopy Center,the First Affiliated Hospital of Jinan University,Guangzhou 510630,China [4]Central Laboratory,School of Medicine,Jinan University,Guangzhou 510632,China

出　　处：《Acta Pharmaceutica Sinica B》2020年第5期837-849,共13页药学学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(81770794 and 314010010);the Special Grants from the Guangzhou Pearl River Young Talents of Science and Technology(201610010079,China);the Fundamental Research Funds for the Central Universities(21617457,China)

摘　　要：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.

关 键 词：IL-27 GHRELIN STAT3 MTOR Food intake 

分 类 号：R589.2[医药卫生—内分泌]