Biglari, Nasim, Gaziano, Isabella, Schumacher, Jonas, Radermacher, Jan, Paeger, Lars, Klemm, Paul ORCID: 0000-0002-5985-1737, Chen, Weiyi, Corneliussen, Svenja, Wunderlich, Claudia M., Sue, Michael, Vollmar, Stefan, Kloeckener, Tim, Sotelo-Hitschfeld, Tamara, Abbasloo, Amin, Edenhofer, Frank, Reimann, Frank ORCID: 0000-0001-9399-6377, Gribble, Fiona M., Fenselau, Henning, Kloppenburg, Peter, Wunderlich, Frank T. and Bruening, Jens C. (2021). Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting. Nat. Neurosci., 24 (7). S. 913 - 930. BERLIN: NATURE PORTFOLIO. ISSN 1546-1726

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Abstract

Pro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus represent key regulators of metabolic homeostasis. Electrophysiological and single-cell sequencing experiments have revealed a remarkable degree of heterogeneity of these neurons. However, the exact molecular basis and functional consequences of this heterogeneity have not yet been addressed. Here, we have developed new mouse models in which intersectional Cre/Dre-dependent recombination allowed for successful labeling, translational profiling and functional characterization of distinct POMC neurons expressing the leptin receptor (Lepr) and glucagon like peptide 1 receptor (Glp1r). Our experiments reveal that POMCLepr+ and POMCGlp1r+ neurons represent largely nonoverlapping subpopulations with distinct basic electrophysiological properties. They exhibit a specific anatomical distribution within the arcuate nucleus and differentially express receptors for energy-state communicating hormones and neurotransmitters. Finally, we identify a differential ability of these subpopulations to suppress feeding. Collectively, we reveal a notably distinct functional microarchitecture of critical metabolism-regulatory neurons. Biglari et al. reveal subgroups of arcuate nucleus hypothalamic neurons that exhibit distinct molecular signatures and feeding-regulatory functions, thus uncovering new regulatory principles in body weight control.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Biglari, NasimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaziano, IsabellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, JonasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radermacher, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paeger, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klemm, PaulUNSPECIFIEDorcid.org/0000-0002-5985-1737UNSPECIFIED
Chen, WeiyiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Corneliussen, SvenjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wunderlich, Claudia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sue, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vollmar, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kloeckener, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sotelo-Hitschfeld, TamaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abbasloo, AminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Edenhofer, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reimann, FrankUNSPECIFIEDorcid.org/0000-0001-9399-6377UNSPECIFIED
Gribble, Fiona M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fenselau, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kloppenburg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wunderlich, Frank T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-591320
DOI: 10.1038/s41593-021-00854-0
Journal or Publication Title: Nat. Neurosci.
Volume: 24
Number: 7
Page Range: S. 913 - 930
Date: 2021
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 1546-1726
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59132

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