Brainstem PrRP neurons mediate the post-prandial effects of cholecystokinin

Amy Worth, Nicolas Nunn, Simon Luckman

Research output: Contribution to conferenceAbstract

Abstract

Prolactin-releasing peptide (PrRP) has a defined role in energy balance: endogenous PrRP is required for the regulation of food intake and adaptive thermogenesis (Dodd et al., 2014, Cell Metab 20: 639). A growing body of evidence suggests that PrRP neurons are essential in mediating satiety signaling, including in response to the gut-produced hormone, cholecystokinin (CCK; Bechtold & Luckman, 2006, Endocrinology 147: 4723). CCK has diverse roles in regulating post-prandial homeostasis: inducing satiety, decreasing gastric motility and restraining post-prandial glucose levels. Here, we propose that PrRP neurons in the nucleus of the solitary tract (NTS) are involved in multiple aspects of CCK signaling in the post-prandial phase in mice. Oral administration of lipid (which is a potent stimulus for CCK release) activates NTS PrRP neurons, as determined by induction of c-Fos protein. Notably, this effect is blocked by IP injection of the CCK1 receptor antagonist, lorglumide. Central administration of PrRP significantly delays gastric emptying and restrains plasma glucose levels following oral administration of glucose. Furthermore, selective activation of NTS PrRP neurons using stimulatory designer receptors (DREADDs) suppresses food intake in a similar manner to CCK. Complementary anterograde and retrograde tracing techniques reveal that NTS PrRP neurons project locally within the dorsal vagal complex, but also to the PVN in the hypothalamus. Thus, NTS PrRP neurons recapitulate multiple aspects of CCK signaling in the post-prandial phase and it is likely that this requires both local and hypothalamic projections.
Original languageEnglish
Publication statusPublished - 12 Jul 2016
EventSSIB 2016 - Porto Congress Centre, Porto, Portugal
Duration: 12 Jul 201616 Jul 2016

Conference

ConferenceSSIB 2016
Country/TerritoryPortugal
CityPorto
Period12/07/1616/07/16

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