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

Research output: Contribution to journalJournal articlepeer-review

  • Mette Q. Ludwig
  • Wenwen Cheng
  • Desiree Gordian
  • Julie Lee
  • Sarah J. Paulsen
  • Stine N. Hansen
  • Egerod, Kristoffer Lihme
  • Pernille Barkholt
  • Christopher J. Rhodes
  • Anna Secher
  • Lotte Bjerre Knudsen
  • Charles Pyke
  • Martin G. Myers
  • Pers, Tune H

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.

Original languageEnglish
JournalNature Metabolism
Volume3
Pages (from-to)530-545
ISSN2522-5812
DOIs
Publication statusPublished - 2021

ID: 260196894