LEAP2 Is an Endogenous Antagonist of the Ghrelin Receptor
| Autor: | Yiyuan Yin, Olivier Dalmas, Hadas Galon-Tilleman, Cristina M. Rondinone, Hui Tian, Maria A. Bednarek, Xuecai Ge, Daniel D. Kaplan, Joshua S. Lichtman, Anish Konkar, Peirong Chen, Hong Yang, Yan Wang, Joseph Grimsby, Lutz Jermutus, Michael Chen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Physiology Growth hormone secretagogue receptor Bariatric Surgery Peptide Endogeny 03 medical and health sciences Eating Mice 0302 clinical medicine Hepcidins Internal medicine Intestine Small medicine Animals Humans Secretion Receptor Receptors Ghrelin Molecular Biology Caloric Restriction chemistry.chemical_classification digestive oral and skin physiology Antagonist Cell Biology Fasting Small intestine Ghrelin Rats 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Liver Growth Hormone Female hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Cell metabolism. 27(2) |
| ISSN: | 1932-7420 |
| Popis: | Summary Ghrelin, an appetite-stimulatory hormone secreted by the stomach, was discovered as a ligand for the growth hormone secretagogue receptor (GHSR). Through GHSR, ghrelin stimulates growth hormone (GH) secretion, a function that evolved to protect against starvation-induced hypoglycemia. Though the biology mediated by ghrelin has been described in great detail, regulation of ghrelin action is poorly understood. Here, we report the discovery of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous antagonist of GHSR. LEAP2 is produced in the liver and small intestine, and its secretion is suppressed by fasting. LEAP2 fully inhibits GHSR activation by ghrelin and blocks the major effects of ghrelin in vivo , including food intake, GH release, and maintenance of viable glucose levels during chronic caloric restriction. In contrast, neutralizing antibodies that block endogenous LEAP2 function enhance ghrelin action in vivo . Our findings reveal a mechanism for fine-tuning ghrelin action in response to changing environmental conditions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|