Endogenous ligands of bovine FFAR2/GPR43 display distinct pharmacological properties
Results show that bFFAR2 presents a dual coupling to Gαi and Gαq and recruits β-arrestin 2 when stimulated with short and medium-chain FFAs up to eight carbons. Straight-chain FFAs with 4 to 7 carbons plus 3-methyl-butanoic acid showed the greatest potency to activate bFFAR2 upstream and downstream signaling, while C2:0, C3:0 and 2-methylpropanoic acid (2MP) were the least potent. 2MP exhibited minimal pharmacological activity towards β-arrestin 2, and although it induced receptor internalization, bFFAR2 trafficking to the early endosome was not observed. Overall, the number of carbons of straight-chain FFAs and methyl position of branched FFAs differentially regulates the activation of bFFAR2.
Authors
- Guillaume Durand (ORCID: https://orcid.org/0000-0001-6655-5904)
- Valérie Lamothe
- Muriel Bonnet (ORCID: https://orcid.org/0000-0001-7193-3543)
- Frédéric Jean‐Alphonse (ORCID: https://orcid.org/0000-0002-7380-5825)
- Éric Reiter (ORCID: https://orcid.org/0000-0002-4631-7439)
- Tainara Cristina Michelotti (ORCID: https://orcid.org/0000-0001-6729-5999)
Institutions
- Université de Tours (FR)
- Centre National de la Recherche Scientifique (FR)
- École Polytechnique (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- École Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (FR)
- Laboratoire de Tribologie et Dynamique des Systèmes (FR)
- Physiologie de la Reproduction et des Comportements (FR)
- Centre Inria de Saclay (FR)
- Unité Mixte de Recherche sur les Herbivores (FR)
Publication Details
- Journal
- Frontiers in Cell and Developmental Biology
- Published
- 2025-08-20
- DOI
- https://doi.org/10.3389/fcell.2025.1645031
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agence Nationale de la Recherche