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A genetic map of the mouse dorsal vagal complex and its role in obesity
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A genetic map of the mouse dorsal vagal complex and its role in obesity
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Journal Article
A genetic map of the mouse dorsal vagal complex and its role in obesity
2021
Overview
The brainstem dorsal vagal complex (DVC) is known to regulate energy balance and is the target of appetite-suppressing hormones, such as glucagon-like peptide 1 (GLP-1). Here we provide a comprehensive genetic map of the DVC and identify neuronal populations that control feeding. Combining bulk and single-nucleus gene expression and chromatin profiling of DVC cells, we reveal 25 neuronal populations with unique transcriptional and chromatin accessibility landscapes and peptide receptor expression profiles. GLP-1 receptor (GLP-1R) agonist administration induces gene expression alterations specific to two distinct sets of
Glp1r
neurons—one population in the area postrema and one in the nucleus of the solitary tract that also expresses calcitonin receptor (
Calcr
). Transcripts and regions of accessible chromatin near obesity-associated genetic variants are enriched in the area postrema and the nucleus of the solitary tract neurons that express
Glp1r
and/or
Calcr
, and activating several of these neuronal populations decreases feeding in rodents. Thus, DVC neuronal populations associated with obesity predisposition suppress feeding and may represent therapeutic targets for obesity.
Ludwig et al. map transcription and chromatin accessibility in single cells across the brainstem dorsal vagal complex, thereby identifying neuronal populations, including some that control feeding.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/43
/ 38/90
/ 64/110
/ 64/60
/ Animals
/ Biomedical and Life Sciences
/ Brain Stem - physiopathology
/ Calcitonin Receptor-Like Protein - genetics
/ Feeding
/ Food
/ Glucagon
/ Glucagon-Like Peptide-1 Receptor - antagonists & inhibitors
/ Humans
/ Male
/ Mice
/ Neurons
/ Obesity
/ Solitary Nucleus - physiology
