Gaziano, Isabella ORCID: 0000-0002-9513-5156, Corneliussen, Svenja ORCID: 0000-0003-2923-0742, Biglari, Nasim, Neuhaus, Rene ORCID: 0000-0002-5810-8386, Shen, Linyan, Sotelo-Hitschfeld, Tamara, Klemm, Paul ORCID: 0000-0002-5985-1737, Steuernagel, Lukas ORCID: 0000-0003-0043-1436, De Solis, Alain J., Chen, Weiyi, Wunderlich, F. Thomas, Kloppenburg, Peter and Bruening, Jens C. (2022). Dopamine-inhibited POMCDrd2+neurons in the ARC acutely regulate feeding and body temperature. JCI Insight, 7 (21). ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 2379-3708

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Abstract

Dopamine acts on neurons in the arcuate nucleus (ARC) of the hypothalamus, which controls homeostatic feeding responses. Here we demonstrate a differential enrichment of dopamine receptor 1 (Drd1) expression in food intake-promoting agouti related peptide (AgRP)/neuropeptide Y (NPY) neurons and a large proportion of Drd2-expressing anorexigenic proopiomelanocortin (POMC) neurons. Owing to the nature of these receptors, this translates into a predominant activation of AgRP/NPY neurons upon dopamine stimulation and a larger proportion of dopamine -inhibited POMC neurons. Employing intersectional targeting of Drd2-expressing POMC neurons, we reveal that dopamine-mediated POMC neuron inhibition is Drd2 dependent and that POMCDrd2+ neurons exhibit differential expression of neuropeptide signaling mediators compared with the global POMC neuron population, which manifests in enhanced somatostatin responsiveness of POMCDrd2+ neurons. Selective chemogenetic activation of POMCDrd2+ neurons uncovered their ability to acutely suppress feeding and to preserve body temperature in fasted mice. Collectively, the present study provides the molecular and functional characterization of POMCDrd2+ neurons and aids our understanding of dopamine-dependent control of homeostatic energy-regulatory neurocircuits.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gaziano, IsabellaUNSPECIFIEDorcid.org/0000-0002-9513-5156UNSPECIFIED
Corneliussen, SvenjaUNSPECIFIEDorcid.org/0000-0003-2923-0742UNSPECIFIED
Biglari, NasimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuhaus, ReneUNSPECIFIEDorcid.org/0000-0002-5810-8386UNSPECIFIED
Shen, LinyanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sotelo-Hitschfeld, TamaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klemm, PaulUNSPECIFIEDorcid.org/0000-0002-5985-1737UNSPECIFIED
Steuernagel, LukasUNSPECIFIEDorcid.org/0000-0003-0043-1436UNSPECIFIED
De Solis, Alain J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, WeiyiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wunderlich, F. ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kloppenburg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-669660
DOI: 10.1172/jci.insight.162753
Journal or Publication Title: JCI Insight
Volume: 7
Number: 21
Date: 2022
Publisher: AMER SOC CLINICAL INVESTIGATION INC
Place of Publication: ANN ARBOR
ISSN: 2379-3708
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
POMC-NEURONS; HYDROXYLASE NEURONS; INTERMEDIATE LOBE; MEDIAN-EMINENCE; GENE-EXPRESSION; RAT PITUITARY; BRAIN-SLICES; WEIGHT-GAIN; LEPTIN; RECEPTORSMultiple languages
Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/66966

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