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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.


Mette Q Ludwig, Wenwen Cheng, Desiree Gordian, Julie Lee, Sarah J Paulsen, Stine N Hansen, Kristoffer L Egerod, Pernille Barkholt, Christopher J Rhodes, Anna Secher, Lotte Bjerre Knudsen, Charles Pyke, Martin G Myers, Tune H Pers. A genetic map of the mouse dorsal vagal complex and its role in obesity. Nature metabolism. 2021 Apr;3(4):530-545

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PMID: 33767443

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