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.
In: Cell Reports, Vol. 43, No. 7, 114509, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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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