An atlas of GPCRs in dopamine neurons: Identification of the free fatty acid receptor 4 as a regulator of food and water intake

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An atlas of GPCRs in dopamine neurons : Identification of the free fatty acid receptor 4 as a regulator of food and water intake. / Apuschkin, Mia; Burm, Hayley B.; Schmidt, Jan H.; Skov, Louise J.; Andersen, Rita C.; Bowin, Carl Fredrik; Støier, Jonatan F.; Jensen, Kathrine L.; Posselt, Leonie P.; Dmytriyeva, Oksana; Sørensen, Andreas T.; Egerod, Kristoffer L.; Holst, Birgitte; Rickhag, Mattias; Schwartz, Thue W.; Gether, Ulrik.

I: Cell Reports, Bind 43, Nr. 7, 114509, 2024.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Apuschkin, M, Burm, HB, Schmidt, JH, Skov, LJ, Andersen, RC, Bowin, CF, Støier, JF, Jensen, KL, Posselt, LP, Dmytriyeva, O, Sørensen, AT, Egerod, KL, Holst, B, Rickhag, M, Schwartz, TW & Gether, U 2024, 'An atlas of GPCRs in dopamine neurons: Identification of the free fatty acid receptor 4 as a regulator of food and water intake', Cell Reports, bind 43, nr. 7, 114509. https://doi.org/10.1016/j.celrep.2024.114509

APA

Apuschkin, M., Burm, H. B., Schmidt, J. H., Skov, L. J., Andersen, R. C., Bowin, C. F., Støier, J. F., Jensen, K. L., Posselt, L. P., Dmytriyeva, O., Sørensen, A. T., Egerod, K. L., Holst, B., Rickhag, M., Schwartz, T. W., & Gether, U. (2024). An atlas of GPCRs in dopamine neurons: Identification of the free fatty acid receptor 4 as a regulator of food and water intake. Cell Reports, 43(7), [114509]. https://doi.org/10.1016/j.celrep.2024.114509

Vancouver

Apuschkin M, Burm HB, Schmidt JH, Skov LJ, Andersen RC, Bowin CF o.a. An atlas of GPCRs in dopamine neurons: Identification of the free fatty acid receptor 4 as a regulator of food and water intake. Cell Reports. 2024;43(7). 114509. https://doi.org/10.1016/j.celrep.2024.114509

Author

Apuschkin, Mia ; Burm, Hayley B. ; Schmidt, Jan H. ; Skov, Louise J. ; Andersen, Rita C. ; Bowin, Carl Fredrik ; Støier, Jonatan F. ; Jensen, Kathrine L. ; Posselt, Leonie P. ; Dmytriyeva, Oksana ; Sørensen, Andreas T. ; Egerod, Kristoffer L. ; Holst, Birgitte ; Rickhag, Mattias ; Schwartz, Thue W. ; Gether, Ulrik. / An atlas of GPCRs in dopamine neurons : Identification of the free fatty acid receptor 4 as a regulator of food and water intake. I: Cell Reports. 2024 ; Bind 43, Nr. 7.

Bibtex

@article{7a5b8b0c16234607a185ceb6122b7a6d,
title = "An atlas of GPCRs in dopamine neurons: Identification of the free fatty acid receptor 4 as a regulator of food and water intake",
abstract = "Midbrain dopaminergic neurons (DANs) are subject to extensive metabotropic regulation, but the repertoire of G protein-coupled receptors (GPCRs) present in these neurons has not been mapped. Here, we isolate DANs from Dat-eGFP mice to generate a GPCR atlas by unbiased qPCR array expression analysis of 377 GPCRs. Combined with data mining of scRNA-seq databases, we identify multiple receptors in DAN subpopulations with 38 of these receptors representing the majority of transcripts. We identify 41 receptors expressed in midbrain DANs but not in non-DAN midbrain cells, including the free fatty acid receptor 4 (FFAR4). Functional expression of FFAR4 is validated by ex vivo Ca2+ imaging, and in vivo experiments support that FFAR4 negatively regulates food and water intake and bodyweight. In addition to providing a critical framework for understanding metabotropic DAN regulation, our data suggest fatty acid sensing by FFAR4 as a mechanism linking high-energy intake to the dopamine-reward pathway.",
keywords = "array analysis, CP: Metabolism, CP: Neuroscience, Dat-eGFP mice, dopamine, fatty acids, FFAR4, fluorescence-activated cell sorting, G protein-coupled receptors, gpr120, heterogeneity, metabolism",
author = "Mia Apuschkin and Burm, {Hayley B.} and Schmidt, {Jan H.} and Skov, {Louise J.} and Andersen, {Rita C.} and Bowin, {Carl Fredrik} and St{\o}ier, {Jonatan F.} and Jensen, {Kathrine L.} and Posselt, {Leonie P.} and Oksana Dmytriyeva and S{\o}rensen, {Andreas T.} and Egerod, {Kristoffer L.} and Birgitte Holst and Mattias Rickhag and Schwartz, {Thue W.} and Ulrik Gether",
note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",
year = "2024",
doi = "10.1016/j.celrep.2024.114509",
language = "English",
volume = "43",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",

}

RIS

TY - JOUR

T1 - An atlas of GPCRs in dopamine neurons

T2 - Identification of the free fatty acid receptor 4 as a regulator of food and water intake

AU - Apuschkin, Mia

AU - Burm, Hayley B.

AU - Schmidt, Jan H.

AU - Skov, Louise J.

AU - Andersen, Rita C.

AU - Bowin, Carl Fredrik

AU - Støier, Jonatan F.

AU - Jensen, Kathrine L.

AU - Posselt, Leonie P.

AU - Dmytriyeva, Oksana

AU - Sørensen, Andreas T.

AU - Egerod, Kristoffer L.

AU - Holst, Birgitte

AU - Rickhag, Mattias

AU - Schwartz, Thue W.

AU - Gether, Ulrik

N1 - Publisher Copyright: © 2024 The Author(s)

PY - 2024

Y1 - 2024

N2 - Midbrain dopaminergic neurons (DANs) are subject to extensive metabotropic regulation, but the repertoire of G protein-coupled receptors (GPCRs) present in these neurons has not been mapped. Here, we isolate DANs from Dat-eGFP mice to generate a GPCR atlas by unbiased qPCR array expression analysis of 377 GPCRs. Combined with data mining of scRNA-seq databases, we identify multiple receptors in DAN subpopulations with 38 of these receptors representing the majority of transcripts. We identify 41 receptors expressed in midbrain DANs but not in non-DAN midbrain cells, including the free fatty acid receptor 4 (FFAR4). Functional expression of FFAR4 is validated by ex vivo Ca2+ imaging, and in vivo experiments support that FFAR4 negatively regulates food and water intake and bodyweight. In addition to providing a critical framework for understanding metabotropic DAN regulation, our data suggest fatty acid sensing by FFAR4 as a mechanism linking high-energy intake to the dopamine-reward pathway.

AB - Midbrain dopaminergic neurons (DANs) are subject to extensive metabotropic regulation, but the repertoire of G protein-coupled receptors (GPCRs) present in these neurons has not been mapped. Here, we isolate DANs from Dat-eGFP mice to generate a GPCR atlas by unbiased qPCR array expression analysis of 377 GPCRs. Combined with data mining of scRNA-seq databases, we identify multiple receptors in DAN subpopulations with 38 of these receptors representing the majority of transcripts. We identify 41 receptors expressed in midbrain DANs but not in non-DAN midbrain cells, including the free fatty acid receptor 4 (FFAR4). Functional expression of FFAR4 is validated by ex vivo Ca2+ imaging, and in vivo experiments support that FFAR4 negatively regulates food and water intake and bodyweight. In addition to providing a critical framework for understanding metabotropic DAN regulation, our data suggest fatty acid sensing by FFAR4 as a mechanism linking high-energy intake to the dopamine-reward pathway.

KW - array analysis

KW - CP: Metabolism

KW - CP: Neuroscience

KW - Dat-eGFP mice

KW - dopamine

KW - fatty acids

KW - FFAR4

KW - fluorescence-activated cell sorting

KW - G protein-coupled receptors

KW - gpr120

KW - heterogeneity

KW - metabolism

U2 - 10.1016/j.celrep.2024.114509

DO - 10.1016/j.celrep.2024.114509

M3 - Journal article

C2 - 39003735

AN - SCOPUS:85198346797

VL - 43

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 7

M1 - 114509

ER -

ID: 399065218