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
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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
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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
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Journal ArticleDOI
Circulating Ghrelin Acts on GABA Neurons of the Area Postrema and Mediates Gastric Emptying in Male Mice
Agustina Cabral,María Paula Cornejo,Gimena Fernandez,Pablo Nicolás de Francesco,Guadalupe Garcia-Romero,Maia Uriarte,Jeffrey M. Zigman,Enrique Leo Portiansky,Mirta Reynaldo,Mario Perello +9 more
TL;DR: It is shown that the capacity of circulating ghrelin to acutely induce gastric emptying in mice requires the integrity of the AP, which contains a population of GABA neurons that are a target of plasma ghrelIn.
Journal ArticleDOI
The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a
Alix A. J. Rouault,Luciana K. Rosselli-Murai,Ciria C. Hernandez,Luis E. Gimenez,Gregory G. Tall,Julien A. Sebag +5 more
TL;DR: It is shown that the accessory protein MRAP2 altered GHSR1a signaling by inhibiting its constitutive activity, as well as by enhancing its G protein–dependent signaling and blocking the recruitment and signaling of β-arrestin in response to ghrelin.
Book ChapterDOI
Obestatin: is it really doing something?
TL;DR: Like ghrelin, obestatin is produced in the gastrointestinal tract, including the pancreas and adipose tissue, and exerts both local actions in peripheral tissues, and distant effects at the central level, suggesting it may indeed be considered a hormone.
Journal ArticleDOI
Low-dose ghrelin infusion--evidence against a hormonal role in food intake.
Florian Lippl,Johannes Erdmann,Amelie Steiger,Nicole Lichter,Cäcilia Czogalla-Peter,Martin Bidlingmaier,Sylvia Tholl,Volker Schusdziarra +7 more
TL;DR: Neither physiological nor moderably supraphysiological ghrelin levels were associated with any change of the various food intake parameters determined and these data do not favour a hormonal role of peripheralghrelin in the regulation of food intake.
Journal ArticleDOI
Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans
Ylva Falkén,Per M. Hellström,Gareth J. Sanger,O. E. Dewit,George E. Dukes,Per Grybäck,Jens J. Holst,Erik Näslund +7 more
TL;DR: The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis during a 6‐h infusion in humans.
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