Plasticity in vagal afferent neurones during feeding and fasting: mechanisms and significance.
The ingestion of food activates mechanisms leading to inhibition of food intake and gastric emptying mediated by the release of regulatory peptides, for example cholecystokinin (CCK), and lipid amides, e.g. oleylethanolamide from the gut. In addition, there are both peptides (e.g. ghrelin) and lipid amides (e.g. anandamide) that appear to signal the absence of food in the gut and that are associated with the stimulation of food intake. Vagal afferent neurones are a common target for both types of signal. Remarkably, the neurochemical phenotype of these neurones itself depends on nutritional status. CCK acting at CCK1 receptors on vagal afferent neurones stimulates expression in these neurones of Y2-receptors and the neuropeptide CART, both of which are associated with the inhibition of food intake. Conversely, in fasted rats when plasma CCK is low, these neurones express cannabinoid (CB)-1 and melanin concentrating hormone (MCH)-1 receptors, and MCH, and this is inhibited by exogenous CCK or endogenous CCK released by refeeding. The stimulation of CART expression by CCK is mediated by the activation of CREB and EGR1; ghrelin inhibits the action of CCK by promoting nuclear exclusion of CREB and leptin potentiates the action of CCK by the stimulation of EGR1 expression. Vagal afferent neurones therefore constitute a level of integration outside the CNS for nutrient-derived signals that control energy intake and that are capable of encoding recent nutrient ingestion.
Physiological Laboratory, School of Biomedical Sciences, University of Liverpool, Crown Street, Liverpool, UK. g.j.dockray@liverpool.ac.uk
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Burdyga
D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D005215:Fasting / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D006801:Humans; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D011984:Sensory Receptor Cells / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*