The controversial role of the vagus nerve in mediating ghrelin's actions: gut feelings and beyond

Mario Perelló; María P Cornejo; Pablo N De Francesco; Gimena Fernandez; Laurent Gautron; Lesly S Valdivia

doi:10.1016/j.ibneur.2022.03.003

The controversial role of the vagus nerve in mediating ghrelin's actions: gut feelings and beyond

IBRO Neurosci Rep. 2022 Mar 12:12:228-239. doi: 10.1016/j.ibneur.2022.03.003. eCollection 2022 Jun.

Authors

Mario Perelló^{1

2}, María P Cornejo¹, Pablo N De Francesco¹, Gimena Fernandez¹, Laurent Gautron³, Lesly S Valdivia¹

Affiliations

¹ Laboratory of Neurophysiology of the Multidisciplinary Institute of Cell Biology [IMBICE, Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA), National University of La Plata], La Plata, Buenos Aires, Argentina.
² Department of Surgical Sciences, Functional Pharmacology and Neuroscience, University of Uppsala, Uppsala, Sweden.
³ Center for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.

Abstract

Ghrelin is a stomach-derived peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) and displays a plethora of neuroendocrine, metabolic, autonomic and behavioral actions. It has been proposed that some actions of ghrelin are exerted via the vagus nerve, which provides a bidirectional communication between the central nervous system and peripheral systems. The vagus nerve comprises sensory fibers, which originate from neurons of the nodose and jugular ganglia, and motor fibers, which originate from neurons of the medulla. Many anatomical studies have mapped GHSR expression in vagal sensory or motor neurons. Also, numerous functional studies investigated the role of the vagus nerve mediating specific actions of ghrelin. Here, we critically review the topic and discuss the available evidence supporting, or not, a role for the vagus nerve mediating some specific actions of ghrelin. We conclude that studies using rats have provided the most congruent evidence indicating that the vagus nerve mediates some actions of ghrelin on the digestive and cardiovascular systems, whereas studies in mice resulted in conflicting observations. Even considering exclusively studies performed in rats, the putative role of the vagus nerve in mediating the orexigenic and growth hormone (GH) secretagogue properties of ghrelin remains debated. In humans, studies are still insufficient to draw definitive conclusions regarding the role of the vagus nerve mediating most of the actions of ghrelin. Thus, the extent to which the vagus nerve mediates ghrelin actions, particularly in humans, is still uncertain and likely one of the most intriguing unsolved aspects of the field.

Keywords: AP, area postrema; ARH, hypothalamic arcuate nucleus; AgRP, agouti-related protein; Amb, nucleus ambiguous; Autonomic nervous system; CART, cocaine, and amphetamine-regulated transcript; CB1, cannabinoid receptor type 1; CCK, cholecystokinin; DMNV, dorsal motor nucleus of the vagus; DVC, dorsal vagal complex; Dorsal vagal complex; ERK, extracellular signal-regulated kinases; GABA, gamma aminobutyric acid; GH, growth hormone; GHSR; GHSR, growth hormone secretagogue receptor; GI, gastrointestinal; GLP 1, glucagon-like peptide 1; Ghrelin receptor; ICV, intracerebroventricularly; IP, intraperitoneally; ISH, in situ hybridization; IV, intravenously; JG, jugular ganglion; LEAP2, liver-expressed antimicrobial peptide 2; MMC, migrating motor complex; NG, nodose ganglion; NTS, nucleus of the solitary tract; Nodose ganglion; PCR, polymerase chain reaction; SC, subcutaneously; TRPV1, transient receptor potential vanilloid receptor 1.

Publication types

Review