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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β1-adrenergic receptors mediate plasma acyl-ghrelin elevation and depressive-like behavior induced by chronic psychosocial stress.
Deepali Gupta,Jen Chieh Chuang,Bharath K. Mani,Kripa Shankar,Juan A. Rodriguez,Sherri Osborne-Lawrence,Nathan P. Metzger,Jeffrey M. Zigman +7 more
TL;DR: It is found that administration of the β1-adrenergic receptor (β1AR) blocker atenolol during CSDS blunts the elevation of plasma acyl-ghrelin and exaggerates depressive-like behavior.
Journal ArticleDOI
Dopamine Receptor Type 2 and Ghrelin Receptor Coexpression Alters CaV2.2 Modulation by G Protein Signaling Cascades.
Santiago Cordisco Gonzalez,Emilio Román Mustafá,Silvia Susana Rodríguez,Mario Perello,Jesica Raingo +4 more
TL;DR: D2R-GHSR co-expression reduces the inhibition of CaV2.2 currents by agonist-induced D2R activation and added a new source of basal CaV 2.2 current inhibition to the one produced by GHSR solely expression, allowing for a novel mechanism for controlling CaV3.2 Currents involving the co- expression of two physiologically relevant GPCRs.
Journal ArticleDOI
Liver Expressed Antimicrobial Peptide 2 is Associated with Steatosis in Mice and Humans.
TL;DR: The study suggests leap2 is associated with hepatic steatosis, which may involve lipolytic/lipogenic pathway and insulin signaling, and circulating LEAP2 is an independent predictor of NAFLD.
Journal ArticleDOI
Identifying key residues and key interactions for the binding of LEAP2 to receptor GHSR1a
TL;DR: New insights are provided into the interaction of LEAP2 with its receptor, and the design of novel ligands for GHSR1a in future studies are facilitated.
Journal ArticleDOI
Ghrelin binding to serum albumin and its biological impact.
Daniela Lufrano,Sebastián A. Trejo,Ramiro E. Llovera,Mariano Salgueiro,Gimena Fernandez,Valentina Martínez Damonte,F. Luis González Flecha,Jesica Raingo,Mario R. Ermácora,Mario R. Ermácora,Mario Perello +10 more
TL;DR: It is suggested that ghrelin binds to serum albumin and that this interaction impacts on the biological activity of the hormone.
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