Exendin-4 decreases ghrelin levels through mTOR signaling.
Exendin-4 (EX-4), a long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist, regulates feeding behavior through its ability to inhibit gastric emptying. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate appetite. Here, we report that EX-4 suppresses ghrelin production through the mTORC1-dependent mechanism. Central administration of EX-4 reduces gastric, hypothalamic and plasma ghrelin in both C57BL/6J mice and diet induced obese mice. These changes were associated with a significant increase in mTORC1 activity. Both GLP-1 and EX-4 suppressed the expression and secretion of ghrelin in cultured mHypoE-42 cells, a hypothalamic cell line. These effects were associated with significant changes in mTOR signaling. Inhibition of mTORC1 activity by mTOR siRNA or rapamycin abolished the suppression of ghrelin production induced by GLP-1 and EX-4 in mHypoE-42 cells. Our results identify mTORC1 as a critical signaling pathway for the downregulation of ghrelin induced by activation of GLP-1R.
['Hong|Xiaosi|X|', 'Zhang|Heng|H|', 'Liang|Hongbin|H|', 'Li|Danjie|D|', 'Huang|Jiana|J|', 'Li|Zhi|Z|', 'Jiang|Sibo|S|', 'Zhang|Weizhen|W|', 'Xu|Geyang|G|']
D000818:Animals D000077270:Exenatide D005753:Gastric Mucosa D054439:Ghrelin D000067757:Glucagon-Like Peptide-1 Receptor D007031:Hypothalamus D007276:Injections, Intraventricular D008297:Male D008810:Mice, Inbred C57BL D010455:Peptides D015398:Signal Transduction D013270:Stomach D058570:TOR Serine-Threonine Kinases D014688:Venoms
Exendin-4 Ghrelin GLP-1R mTORC1 GLP-1 Food intake