Expression of glucagon-like peptide 1 receptor in neuropeptide Y neurons of the arcuate nucleus in mice

Oct 1, 2021Brain structure & function

Presence of glucagon-like peptide 1 receptors in appetite-regulating neurons of the mouse brain’s arcuate nucleus

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Abstract

Approximately 20% of neuropeptide Y (NPY) neurons in the arcuate nucleus express GLP-1 receptors.

GLP-1 receptors are present on NPY neurons in the arcuate nucleus, indicating a potential direct action of GLP-1 on these orexigenic neurons.
GLP-1 receptor immunoreactivity is found in the outer membrane of NPY neuron cell bodies and in axons forming synapses with these neurons.
Inhibitory synapses from GLP-1 receptor-containing neurons target NPY neurons, suggesting a mechanism for GLP-1's influence on appetite regulation.
The findings indicate that GLP-1 signaling may modulate NPY neurons through both direct receptor interaction and indirect synaptic connections.

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Glucagon-like peptide 1 (GLP-1) and its agonists exert anorexigenic effect at least partly via acting on GLP-1 receptors (GLP-1R) in the arcuate nucleus (ARC). While the anorexigenic, proopiomelanocortin (POMC) neurons of the ARC were shown previously to express GLP-1R, the putative GLP-1R-content of the orexigenic, neuropeptide Y (NPY) neurons remained so far undetected. As GLP-1R is abundant in the ventromedial ARC, where NPY neurons are located; here, we address the possibility that GLP-1 can act directly on the orexigenic NPY system via GLP-1R. Double-labeling immunocytochemistry and in situ hybridization were performed on tissues of adult male mice to detect GLP-1R in NPY neurons. In double-immunolabeled preparations, GLP-1R-immunoreactivity was observed in NPY neurons and in axons ensheathing the majority of NPY neurons. Ultrastructural studies confirmed that GLP-1R-immunoreactivity is associated with the outer membrane of NPY perikarya as well as with axons forming symmetric type, inhibitory synapses on NPY-containing neurons. Double-labeling in situ hybridization experiments demonstrated the expression of GLP-1R mRNA in approximately 20% of NPY mRNA-containing neurons of the ARC. In summary, our data demonstrate the presence of GLP-1R protein and mRNA in NPY neurons of ARC and also reveal the innervation of NPY neurons by GLP-1R-containing inhibitory neurons. These observations suggest that GLP-1 signaling can influence NPY neurons both directly and indirectly. Furthermore, GLP-1 signaling on energy homeostasis appears to involve both direct and indirect effects of GLP-1 on the orexigenic NPY neurons, in addition to the previously known effects via the anorexigenic POMC neuronal system.

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Expression of glucagon-like peptide 1 receptor in neuropeptide Y neurons of the arcuate nucleus in mice

Abstract

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