Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402:656–60.
Article CAS PubMed Google Scholar
Frühbeck G, Díez Caballero A, Gil MJ. Fundus functionality and ghrelin concentrations after bariatric surgery. N Engl J Med. 2004;350:308–9.
Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273:974–7.
Article CAS PubMed Google Scholar
Adriaenssens AE, Svendsen B, Lam BY, Yeo GS, Holst JJ, Reimann F, et al. Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets. Diabetologia. 2016;59:2156–65.
Article CAS PubMed PubMed Central Google Scholar
Holst B, Cygankiewicz A, Jensen TH, Ankersen M, Schwartz TW. High constitutive signaling of the ghrelin receptor–identification of a potent inverse agonist. Mol Endocrinol. 2003;17:2201–10.
Article CAS PubMed Google Scholar
Dass NB, Munonyara M, Bassil AK, Hervieu GJ, Osbourne S, Corcoran S, et al. Growth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin. Neuroscience. 2003;120:443–53.
Article CAS PubMed Google Scholar
Rodríguez A, Gómez-Ambrosi J, Catalán V, Gil MJ, Becerril S, Sáinz N, et al. Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Int J Obes. 2009;33:541–52.
Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes. 2001;50:1714–9.
Article CAS PubMed Google Scholar
Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature. 2000;407:908–13.
Pfluger PT, Kirchner H, Gunnel S, Schrott B, Perez-Tilve D, Fu S, et al. Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure. Am J Physiol Gastrointest Liver Physiol. 2008;294:G610–8.
Article CAS PubMed Google Scholar
St-Pierre DH, Karelis AD, Cianflone K, Conus F, Mignault D, Rabasa-Lhoret R, et al. Relationship between ghrelin and energy expenditure in healthy young women. J Clin Endocrinol Metab. 2004;89:5993–7.
Article CAS PubMed Google Scholar
Mani BK, Uchida A, Lee Y, Osborne-Lawrence S, Charron MJ, Unger RH, et al. Hypoglycemic effect of combined ghrelin and glucagon receptor blockade. Diabetes. 2017;66:1847–57.
Article CAS PubMed PubMed Central Google Scholar
Tong J, Prigeon RL, Davis HW, Bidlingmaier M, Kahn SE, Cummings DE, et al. Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans. Diabetes. 2010;59:2145–51.
Article CAS PubMed PubMed Central Google Scholar
Zhao TJ, Liang G, Li RL, Xie X, Sleeman MW, Murphy AJ, et al. Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice. Proc Natl Acad Sci USA. 2010;107:7467–72.
Article CAS PubMed PubMed Central Google Scholar
Al Massadi O, Nogueiras R, Dieguez C, Girault JA. Ghrelin and food reward. Neuropharmacology. 2019;148:131–8.
Article CAS PubMed Google Scholar
Dickson SL, Egecioglu E, Landgren S, Skibicka KP, Engel JA, Jerlhag E. The role of the central ghrelin system in reward from food and chemical drugs. Mol Cell Endocrinol. 2011;340:80–7.
Article CAS PubMed Google Scholar
Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001;50:707–9.
Pöykkö SM, Kellokoski E, Hörkkö S, Kauma H, Kesäniemi YA, Ukkola O. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes. 2003;52:2546–53.
Schöfl C, Horn R, Schill T, Schlosser HW, Müller MJ, Brabant G. Circulating ghrelin levels in patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87:4607–10.
Ezquerro S, Mocha F, Frühbeck G, Guzmán-Ruiz R, Valentí V, Mugueta C, et al. Ghrelin reduces TNF-α-induced human hepatocyte apoptosis, autophagy, and pyroptosis: role in obesity-associated NAFLD. J Clin Endocrinol Metab. 2019;104:21–37.
Marchesini G, Pagotto U, Bugianesi E, De Iasio R, Manini R, Vanni E, et al. Low ghrelin concentrations in nonalcoholic fatty liver disease are related to insulin resistance. J Clin Endocrinol Metab. 2003;88:5674–9.
Article CAS PubMed Google Scholar
Krause A, Sillard R, Kleemeier B, Kluver E, Maronde E, Conejo-Garcia JR, et al. Isolation and biochemical characterization of LEAP-2, a novel blood peptide expressed in the liver. Protein Sci. 2003;12:143–52.
Article CAS PubMed PubMed Central Google Scholar
Ge X, Yang H, Bednarek MA, Galon-Tilleman H, Chen P, Chen M, et al. LEAP2 is an endogenous antagonist of the ghrelin receptor. Cell Metab. 2018;27(461–9):e6.
Howard A, Townes C, Milona P, Nile CJ, Michailidis G, Hall J. Expression and functional analyses of liver expressed antimicrobial peptide-2 (LEAP-2) variant forms in human tissues. Cell Immunol. 2010;261:128–33.
Article CAS PubMed Google Scholar
Francisco V, Tovar S, Conde J, Pino J, Mera A, Lago F, et al. Levels of the novel endogenous antagonist of ghrelin receptor, liver-enriched antimicrobial peptide-2, in patients with rheumatoid arthritis. Nutrients. 2020;12:1006. https://doi.org/10.3390/nu12041006
Sakai K, Shiomi K, Mochizuki H, Islam MN, Nabekura H, Tanida R, et al. Human liver-expressed antimicrobial peptide 2 elevation in the cerebrospinal fluid in bacterial meningitis. Brain Behav. 2021;11:e02111.
Article CAS PubMed PubMed Central Google Scholar
Mani BK, Puzziferri N, He Z, Rodriguez JA, Osborne-Lawrence S, Metzger NP, et al. LEAP2 changes with body mass and food intake in humans and mice. J Clin Invest. 2019;129:3909–23.
Article PubMed PubMed Central Google Scholar
M’Kadmi C, Cabral A, Barrile F, Giribaldi J, Cantel S, Damian M, et al. N-terminal liver-expressed antimicrobial peptide 2 (LEAP2) region exhibits inverse agonist activity toward the ghrelin receptor. J Med Chem. 2019;62:965–73.
Islam MN, Mita Y, Maruyama K, Tanida R, Zhang W, Sakoda H, et al. Liver-expressed antimicrobial peptide 2 antagonizes the effect of ghrelin in rodents. J Endocrinol. 2020;244:13–23.
Article CAS PubMed PubMed Central Google Scholar
Lugilde J, Casado S, Beiroa D, Cuñarro J, Garcia-Lavandeira M, Álvarez CV, et al. LEAP-2 counteracts ghrelin-induced food Intake in a nutrient, growth hormone and age independent manner. Cells. 2022;11:324.
Article CAS PubMed PubMed Central Google Scholar
Ezquerro S, Tuero C, Becerril S, Valentí V, Moncada R, Landecho MF, et al. Antagonic effect of ghrelin and LEAP-2 on hepatic stellate cell activation and liver fibrosis in obesity-associated nonalcoholic fatty liver disease. Eur J Endocrinol. 2023;188:564–77.
Çakar S, Arslan N, Ateş M, Sayin O, Akyaz O, Tatar Arik T, et al. Serum LEAP-2 as a potential biomarker for hepatic steatosis in adolescents with obesity and MASLD: a cross-sectional study. Diagnostics (Basel). 2025;15:2816. https://doi.org/10.3390/diagnostics15212816
Gahete MD, Rincón-Fernández D, Villa-Osaba A, Hormaechea-Agulla D, Ibáñez-Costa A, Martínez-Fuentes AJ, et al. Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight. J Endocrinol. 2014;220:R1-24.
Comments (0)