Interleukin-27 decreases ghrelin production through signal transducer and activator of transcription 3-mechanistic target of rapamycin signaling.
10.1016/j.apsb.2019.12.018
- Author:
Heng ZHANG
1
;
Qingjie LI
1
;
Yuxin TENG
1
;
Yubi LIN
2
;
Shaojian LI
1
;
Tingfeng QIN
1
;
Linxi CHEN
1
;
Jiana HUANG
1
;
Hening ZHAI
3
;
Quan YU
4
;
Geyang XU
1
Author Information
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.
- Publication Type:Journal Article
- Keywords:
DIO, diet-induced-obese;
Food intake;
Ghrelin;
IFN-γ, interferon gamma;
IL-27;
IL-27, interleukin-27;
S6, ribosomal protein subunit 6;
S6K, ribosomal protein subunit 6 kinase;
STAT3;
STAT3, signal transducer and activator of transcription 3;
WSX-1, interleukin 27 receptor subunit alpha;
mTOR;
mTOR, mechanistic target of rapamycin
- From:
Acta Pharmaceutica Sinica B
2020;10(5):837-849
- CountryChina
- Language:English
-
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 siRNA or rapamycin blocked the suppression of ghrelin production induced by IL-27 in mHypoE-N42 cells. 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.
