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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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.

Original languageEnglish
Article number114509
JournalCell Reports
Volume43
Issue number7
Number of pages23
ISSN2211-1247
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

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

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