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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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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The role of ghrelin in reward-based eating.
Mario Perello,Jeffrey M. Zigman +1 more
TL;DR: Ghrelin's orexigenic actions, the evidence linking gh Relin to food reward behavior, potential mechanisms by which ghrelin mediates reward-based eating behavior, and those studies suggesting an obligatory role for ghrelIn in the changed eating behaviors induced by stress are reviewed.
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Ghrelin signalling on food reward: a salient link between the gut and the mesolimbic system.
Mario Perello,Suzanne L. Dickson +1 more
TL;DR: A variety of studies are reviewed that support the notion that ghrelin signalling at the level of the mesolimbic system is one of the key molecular substrates that provides a physiological signal connecting gut and reward pathways.
Journal ArticleDOI
Therapeutic Potential of Targeting the Ghrelin Pathway
TL;DR: The aim of this review is to discuss and highlight the broad pharmacological potential of ghrelin pathway modulation for the treatment of anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, renal and pulmonary disease, gastrointestinal (GI) disorders, inflammatory disorders and metabolic syndrome.
Journal ArticleDOI
Obesity Impairs the Action of the Neuroendocrine Ghrelin System
TL;DR: Interestingly, weight loss restores ghrelin secretion and function, and it is hypothesized that ghrelIn resistance is a mechanism designed to protect a higher body weight set-point established during times of food availability, to maximize energy reserves during a time of food scarcity.
Journal ArticleDOI
Ghrelin Interacts with Human Plasma Lipoproteins
TL;DR: It is reported that the presence of the acyl group is necessary for ghrelin interaction with TRLs and LDLs but not HDLs and VHDLs.
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