The ups and downs of growth hormone secretagogue receptor signaling
María Paula Cornejo,Emilio Román Mustafá,Daniela Cassano,Jean-Louis Banères,Jesica Raingo,Mario Perello +5 more
Reads0
Chats0
TLDR
The growth hormone secretagogue receptor (GHSR) has emerged as one of the most fascinating molecules from the perspective of neuroendocrine control as mentioned in this paper, and plays key roles regulating not only growth hormone secretion but also food intake, adiposity, body weight, glucose homeostasis and other complex functions.Abstract:
The growth hormone secretagogue receptor (GHSR) has emerged as one of the most fascinating molecules from the perspective of neuroendocrine control. GHSR is mainly expressed in the pituitary and the brain, and plays key roles regulating not only growth hormone secretion but also food intake, adiposity, body weight, glucose homeostasis and other complex functions. Quite atypically, GHSR signaling displays a basal constitutive activity that can be up- or downregulated by two digestive system-derived hormones: the octanoylated-peptide ghrelin and the liver-expressed antimicrobial peptide 2 (LEAP2), which was recently recognized as an endogenous GHSR ligand. The existence of two ligands with contrary actions indicates that GHSR activity can be tightly regulated and that the receptor displays the capability to integrate such opposing inputs in order to provide a balanced intracellular signal. This article provides a summary of the current understanding of the biology of ghrelin, LEAP2 and GHSR and discusses the reconceptualization of the cellular and physiological implications of the ligand-regulated GHSR signaling, based on the latest findings.read more
Citations
More filters
Journal ArticleDOI
LEAP2 deletion in mice enhances ghrelin's actions as an orexigen and growth hormone secretagogue.
Kripa Shankar,Nathan P. Metzger,Omprakash Singh,Bharath K. Mani,Sherri Osborne-Lawrence,Salil Varshney,Deepali Gupta,Sean B. Ogden,Shota Takemi,Corine P. Richard,Karabi Nandy,Chen Liu,Jeffrey M. Zigman +12 more
TL;DR: The first known LEAP2-KO mouse line was generated in this paper, where the metabolic effects of genetic leaper-expressed antimicrobial peptide-2 (LEAP2) deletion were determined.
Journal ArticleDOI
LEAP2 reduces postprandial glucose excursions and ad libitum food intake in healthy men
Christoffer A. Hagemann,Malene Shin Jensen,Stephanie Holm,Lærke S. Gasbjerg,Sarah Byberg,Kirsa Skov-Jeppesen,Bolette Hartmann,Jens J. Holst,Flemming Dela,Tina Vilsbøll,Mikkel B. Christensen,Birgitte Holst,Filip K. Knop +12 more
TL;DR: The authors investigated the effects of exogenous LEAP2 on post-prandial glucose metabolism and ad libitum food intake in a randomized, double-blind, placebo-controlled, crossover trial of 20 healthy men.
Journal ArticleDOI
Circulating ghrelin crosses the blood-cerebrospinal fluid barrier via growth hormone secretagogue receptor dependent and independent mechanisms.
Maia Uriarte,Pablo Nicolás de Francesco,Gimena Fernandez,Daniel Castrogiovanni,Micaela D'Arcangelo,Monica Imbernon,Sonia Cantel,Séverine Denoyelle,Jean-Alain Fehrentz,Jeppe Praetorius,Vincent Prevot,Mario Perello +11 more
TL;DR: In this paper, a variety of in vivo and in vitro studies were performed to test the hypothesis that the transport of ghrelin across the blood-CSF barrier occurs in a GHSR-dependent manner.
Journal ArticleDOI
LEAP2 Impairs the Capability of the Growth Hormone Secretagogue Receptor to Regulate the Dopamine 2 Receptor Signaling.
Emilio Román Mustafá,Santiago Cordisco Gonzalez,Marjorie Damian,Sonia Cantel,Séverine Denoyelle,Renaud Wagner,Helgi B. Schiöth,Helgi B. Schiöth,Jean-Alain Fehrentz,Jean-Louis Banères,Mario Perello,Jesica Raingo +11 more
TL;DR: In this article, the role of LEAP2 on the canonical and non-canonical modes of action of GHSR on voltage-gated calcium channels type 2.2 (CaV2.2) was investigated.
Journal ArticleDOI
The controversial role of the vagus nerve in mediating ghrelin's actions: gut feelings and beyond
Mario Perello,María Paula Cornejo,Pablo Nicolás de Francesco,Gimena Fernandez,Laurent Gautron,Lesly S Valdivia +5 more
TL;DR: In this paper , the authors discuss the available evidence supporting, or not, a role for the vagus nerve mediating some specific actions of ghrelin, and conclude that studies using rats have provided the most congruent evidence indicating that the VN mediates some actions of Ghrelin on the digestive and cardiovascular systems, whereas studies in mice resulted in conflicting observations.
References
More filters
Journal ArticleDOI
High constitutive signaling of the ghrelin receptor--identification of a potent inverse agonist.
TL;DR: It is concluded that the ghrelin receptor is highly constitutively active and that this activity could be of physiological importance in its role as a regulator of both GH secretion and appetite control.
Journal ArticleDOI
Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference.
Katherine E. Wortley,Keith D. Anderson,Karen Garcia,Jane D. Murray,Lubomira Malinova,Rong Liu,Marshena Moncrieffe,Karen Thabet,Hilary J. Cox,George D. Yancopoulos,Stanley J. Wiegand,Mark W. Sleeman +11 more
TL;DR: Ex vivo analyses of ghrl(-/-) mice demonstrate that endogenous ghrelin plays a prominent role in determining the type of metabolic substrate that is used for maintenance of energy balance, particularly under conditions of high fat intake.
Journal ArticleDOI
Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice
Tong Jin Zhao,Guosheng Liang,Robert Lin Li,Xuefen Xie,Mark W. Sleeman,Andrew J. Murphy,David M. Valenzuela,George D. Yancopoulos,Joseph L. Goldstein,Michael S. Brown +9 more
TL;DR: Infusion of either ghrelin or GH normalized blood glucose in Goat−/− mice and prevented death, thereby preserving blood glucose and preventing death.
Journal ArticleDOI
GOAT links dietary lipids with the endocrine control of energy balance
Henriette Kirchner,Jesus A. Gutierrez,Patricia J. Solenberg,Paul T. Pfluger,Traci A. Czyzyk,Jill A. Willency,Annette Schürmann,HG Joost,Ronald J. Jandacek,John E. Hale,Mark L. Heiman,Matthias H. Tschöp +11 more
TL;DR: Ghrelin O-acyl transferase (GOAT), which is essential for ghrelin acylation, is regulated by nutrient availability, depends on specific dietary lipids as acylated substrates and links ingested lipids to energy expenditure and body fat mass.
Journal ArticleDOI
Ghrelin Directly Interacts With Neuropeptide-Y-Containing Neurons in the Rat Arcuate Nucleus: Ca2+ Signaling via Protein Kinase A and N-Type Channel-Dependent Mechanisms and Cross-Talk With Leptin and Orexin
TL;DR: Results demonstrate that ghrelin directly interacts with NPY neurons in the ARC to induce Ca( 2+) signaling via PKA and N-type Ca(2+) channel-dependent mechanisms.
Related Papers (5)
Growth Hormone Secretagogue Receptor Dimers: A New Pharmacological Target
Martin Wellman,Alfonso Abizaid +1 more