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. 2021 Apr;3(4):530-545.
doi: 10.1038/s42255-021-00363-1. Epub 2021 Mar 25.

A genetic map of the mouse dorsal vagal complex and its role in obesity

Mette Q Ludwig  1 , Wenwen Cheng  2 , Desiree Gordian  2 , Julie Lee  3 , Sarah J Paulsen  4 , Stine N Hansen  4 , Kristoffer L Egerod  1 , Pernille Barkholt  5 , Christopher J Rhodes  6 , Anna Secher  4 , Lotte Bjerre Knudsen  4 , Charles Pyke  4 , Martin G Myers Jr  2 , Tune H Pers  7
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A genetic map of the mouse dorsal vagal complex and its role in obesity

Mette Q Ludwig et al. Nat Metab. 2021 Apr.

Abstract

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.

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