Toward a consensus nomenclature for ghrelin, its non‐acylated form, liver expressed antimicrobial peptide 2 and growth hormone secretagogue receptor

The stomach‐derived octanoylated peptide ghrelin was discovered in 1999 and recognized as an endogenous agonist of the growth hormone secretagogue receptor (GHSR). Subsequently, ghrelin has been shown to play key roles in controlling not only growth hormone secretion, but also a variety of other physiological functions including, but not limited to, food intake, reward‐related behaviors, glucose homeostasis and gastrointestinal tract motility. Importantly, a non‐acylated form of ghrelin, desacyl‐ghrelin, can also be detected in biological samples. Desacyl‐ghrelin, however, does not bind to GHSR at physiological levels, and its physiological role has remained less well‐characterized than that of ghrelin. Ghrelin and desacyl‐ghrelin are currently referred to in the literature using many different terms, highlighting the need for a consistent nomenclature. The variability of terms used to designate ghrelin can lead not only to confusion, but also to miscommunication, especially for those who are less familiar with the ghrelin literature. Thus, we conducted a survey among experts who have contributed to the ghrelin literature aiming to identify whether a consensus may be reached. Based on the results of this consensus, we propose using the terms “ghrelin” and “desacyl‐ghrelin” to refer to the hormone itself and its non‐acylated form, respectively. Based on the results of this consensus, we further propose using the terms “GHSR” for the receptor, and “LEAP2” for liver‐expressed antimicrobial peptide 2, a recently recognized endogenous GHSR antagonist/inverse agonist.

[1]  L. Leggio,et al.  From "Hunger Hormone" to "It's Complicated": Ghrelin Beyond Feeding Control. , 2022, Physiology.

[2]  Cody J. Wenthur,et al.  Complexes of Ghrelin GHS-R1a, GHS-R1b, and Dopamine D1 Receptors Localized in the Ventral Tegmental Area as Main Mediators of the Dopaminergic Effects of Ghrelin , 2021, The Journal of Neuroscience.

[3]  J. Banères,et al.  The ups and downs of growth hormone secretagogue receptor signaling , 2021, The FEBS journal.

[4]  M. Perelló,et al.  THE INTRIGUING LIGAND-DEPENDENT AND LIGAND-INDEPENDENT ACTIONS OF THE GROWTH HORMONE SECRETAGOGUE RECEPTOR ON REWARD-RELATED BEHAVIORS , 2020, Neuroscience & Biobehavioral Reviews.

[5]  L. Leggio,et al.  Ghrelin: From a gut hormone to a potential therapeutic target for alcohol use disorder , 2019, Physiology & Behavior.

[6]  J. Zigman,et al.  Ghrelin's Relationship to Blood Glucose. , 2019, Endocrinology.

[7]  S. Cantel,et al.  N-Terminal Liver-Expressed Antimicrobial Peptide 2 (LEAP2) Region Exhibits Inverse Agonist Activity toward the Ghrelin Receptor. , 2018, Journal of medicinal chemistry.

[8]  V. Voon,et al.  Stress, Motivation, and the Gut–Brain Axis: A Focus on the Ghrelin System and Alcohol Use Disorder , 2018, Alcoholism, clinical and experimental research.

[9]  D. Kaplan LEAP2 is an Endogenous Antagonist of the Ghrelin Receptor , 2018 .

[10]  B. Wiese,et al.  A modified Delphi study to determine the level of consensus across the European Union on the structures, processes and desired outcomes of the management of polypharmacy in older people , 2017, PloS one.

[11]  D. J. Driscoll,et al.  Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi syndrome , 2016, The Journal of clinical investigation.

[12]  M. Perelló,et al.  Ghrelin Signalling on Food Reward: A Salient Link Between the Gut and the Mesolimbic System , 2015, Journal of neuroendocrinology.

[13]  B. Mouillac,et al.  Heterodimerization with its splice variant blocks the ghrelin receptor 1a in a nonsignaling conformation. A study with a purified heterodimer assembled into lipid discs.* , 2013 .

[14]  Kenneth Rockwood,et al.  Searching for an operational definition of frailty: a Delphi method based consensus statement: the frailty operative definition-consensus conference project. , 2013, The journals of gerontology. Series A, Biological sciences and medical sciences.

[15]  J. Goldstein,et al.  Surviving starvation: essential role of the ghrelin-growth hormone axis , 2012, BMC Proceedings.

[16]  H. Ariyasu,et al.  Analysis of plasma ghrelin in patients with medium-chain acyl-CoA dehydrogenase deficiency and glutaric aciduria type II. , 2012, European journal of endocrinology.

[17]  S. Dickson,et al.  The role of the central ghrelin system in reward from food and chemical drugs , 2011, Molecular and Cellular Endocrinology.

[18]  M. Luijendijk,et al.  Acute and chronic suppression of the central ghrelin signaling system reveals a role in food anticipatory activity , 2011, European Neuropsychopharmacology.

[19]  D. Witcher,et al.  Novel ghrelin assays provide evidence for independent regulation of ghrelin acylation and secretion in healthy young men. , 2008, The Journal of clinical endocrinology and metabolism.

[20]  M. Kojima The discovery of ghrelin — A personal memory , 2008, Regulatory Peptides.

[21]  Xiaorong Zhu,et al.  On the Processing of Proghrelin to Ghrelin* , 2006, Journal of Biological Chemistry.

[22]  S. Woods,et al.  Effects of a fixed meal pattern on ghrelin secretion: evidence for a learned response independent of nutrient status. , 2006, Endocrinology.

[23]  R. Neubig,et al.  International Union of Pharmacology. LVI. Ghrelin Receptor Nomenclature, Distribution, and Function , 2005, Pharmacological Reviews.

[24]  K. Kangawa,et al.  Ghrelin: structure and function. , 2005, Physiological reviews.

[25]  D. Chapelot,et al.  Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. , 2004, American journal of physiology. Endocrinology and metabolism.

[26]  N. Kohno,et al.  Increased plasma ghrelin level in lung cancer cachexia. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[27]  S. Wattler,et al.  Isolation and biochemical characterization of LEAP‐2, a novel blood peptide expressed in the liver , 2003, Protein science : a publication of the Protein Society.

[28]  M. Nakazato,et al.  Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats. , 2002, The Journal of endocrinology.

[29]  M. Tschöp,et al.  Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. , 2001, European journal of endocrinology.

[30]  K. Hosoda,et al.  Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. , 2001, The Journal of clinical endocrinology and metabolism.

[31]  B. Wisse,et al.  A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. , 2001, Diabetes.

[32]  K. Kangawa,et al.  Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. , 2000, Biochemical and biophysical research communications.

[33]  S. Bloom,et al.  The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. , 2000, Endocrinology.

[34]  M. Tschöp,et al.  Ghrelin induces adiposity in rodents , 2000, Nature.

[35]  K. Kangawa,et al.  Ghrelin stimulates gastric acid secretion and motility in rats. , 2000, Biochemical and biophysical research communications.

[36]  Peter Schulz-Knappe,et al.  LEAP‐1, a novel highly disulfide‐bonded human peptide, exhibits antimicrobial activity , 2000, FEBS letters.

[37]  C. Tomasetto,et al.  Identification and characterization of a novel gastric peptide hormone: the motilin-related peptide. , 2000, Gastroenterology.

[38]  K. Kangawa,et al.  Purification and Characterization of Rat des-Gln14-Ghrelin, a Second Endogenous Ligand for the Growth Hormone Secretagogue Receptor* , 2000, The Journal of Biological Chemistry.

[39]  M. Nakazato,et al.  Ghrelin is a growth-hormone-releasing acylated peptide from stomach , 1999, Nature.

[40]  Roy G. Smith,et al.  Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. , 1997, Brain research. Molecular brain research.

[41]  Patrick R. Griffin,et al.  A Receptor in Pituitary and Hypothalamus That Functions in Growth Hormone Release , 1996, Science.