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. / Ludwig, Mette Q.; Cheng, Wenwen; Gordian, Desiree; Lee, Julie; Paulsen, Sarah J.; Hansen, Stine N.; Egerod, Kristoffer L.; Barkholt, Pernille; Rhodes, Christopher J.; Secher, Anna; Knudsen, Lotte Bjerre; Pyke, Charles; Myers, Martin G.; Pers, Tune H.
In: Nature Metabolism, Vol. 3, 2021, p. 530-545.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A genetic map of the mouse dorsal vagal complex and its role in obesity
AU - Ludwig, Mette Q.
AU - Cheng, Wenwen
AU - Gordian, Desiree
AU - Lee, Julie
AU - Paulsen, Sarah J.
AU - Hansen, Stine N.
AU - Egerod, Kristoffer L.
AU - Barkholt, Pernille
AU - Rhodes, Christopher J.
AU - Secher, Anna
AU - Knudsen, Lotte Bjerre
AU - Pyke, Charles
AU - Myers, Martin G.
AU - Pers, Tune H.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1038/s42255-021-00363-1
DO - 10.1038/s42255-021-00363-1
M3 - Journal article
C2 - 33767443
AN - SCOPUS:85103174373
VL - 3
SP - 530
EP - 545
JO - Nature Metabolism
JF - Nature Metabolism
SN - 2522-5812
ER -
ID: 260196894