title: Exendin-4 decreases ghrelin levels through mTOR signaling.
abstract: 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.
authors: Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China.
authors: Xiaosi
authors: X
authors: Hong
authors: Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China.
authors: Heng
authors: H
authors: Zhang
authors: Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China.
authors: Hongbin
authors: H
authors: Liang
authors: Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China.
authors: Danjie
authors: D
authors: Li
authors: Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China.
authors: Jiana
authors: J
authors: Huang
authors: Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China.
authors: Zhi
authors: Z
authors: Li
authors: Departments of Pharmaceutics, University of Florida, 6550 Sanger Rd, Orlando, FL 32827, USA.
authors: Sibo
authors: S
authors: Jiang
authors: Shenzhen University Diabetes Center, Shenzhen University Health Science Center, Shenzhen, Guangdong, China; Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109-0346, USA. Electronic address: weizhenz@umich.edu.
authors: Weizhen
authors: W
authors: Zhang
authors: Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China. Electronic address: xugeyangliang@163.com.
authors: Geyang
authors: G
authors: Xu
mesh_terms: D000818:Animals; D000077270:Exenatide; D005753:Gastric Mucosa / Q000378:metabolism; D054439:Ghrelin / Q000096:biosynthesis / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D054439:Ghrelin; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D058570:TOR Serine-Threonine Kinases
keywords: Exendin-4; Food intake; GLP-1; GLP-1R; Ghrelin; mTORC1