Abstract
Glucagon-like peptide-1 (GLP-1) is both a peripherally expressed incretin and a centrally active neuropeptide. Brain derived GLP-1, produced in preproglucagon (PPG) neurons located in the nucleus of the solitary tract (NTS) and projecting to numerous brain regions, is ideally placed to activate central GLP-1 receptors in a range of autonomic control areas. In vivo analysis of central GLP-1 using GLP-1 receptor antagonists has demonstrated the control of a range of feeding responses mediated by GLP-1 receptor activation. Recent advances enabling identification and targeting of the neurons in the NTS has specifically implicated PPG neurons at the core of GLP-1 dependent central and peripheral control for short-term and long-term energy balance.
Highlights
Introduction ‘Gut hormones’ have increasingly been implicated in brain function [1,2]
For this to be the case, there has to be anatomical evidence that the distribution of PPG cell axons and glucagon-like peptide-1 (GLP-1) release sites matches the distribution of GLP-1 receptors in brain, functional evidence of endogenous release of GLP-1 within the CNS, and proof that inhibition or destruction of these PPG neurons prevents the central effects attributed to GLP-1
What inputs do GLP-1 neurons receive? Until the development of the PPG-YFP mouse by Reimann and colleagues [23], PPG neurons could only be identified post hoc by immunocytochemistry. This limited functional analysis of this cell population to the use of immunoreactivity to c-fos or equivalent markers of neuronal activation [15,50,51]. Such studies demonstrated that PPG neurons were activated by gastric distension [51], leptin [52], LiCl and oxytocin [53], placing the PPG neurons at the core of central GLP-1 effects observed in relation to these stimuli
Summary
Introduction ‘Gut hormones’ have increasingly been implicated in brain function [1,2]. These anatomical findings suggest that projections from PPG neurons are appropriately placed to elicit effects on the vast majority of GLP-1 receptors expressed in the CNS.
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