Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids
Abstract
Short-chain fatty acids (SCFAs) have long been known to exert cellular effects on blood leukocytes. Acetate, propionate, and butyrate represent the most capable SCFA, inducing calcium mobilization which subsequently regulates leukocyte function in the immune system. We have cloned the previously described putative orphan G-protein coupled receptor, GPR43, and have functionally identified SCFA as the activating ligands. Acetate and propionate were found to be the two most potent ligands, although butyrate, formate, and valerate (in this order of potency) also were able to induce receptor activation. Both the human and mouse receptor homologues were found to share the same pattern of ligand activation. This finding, together with a high degree of amino acid sequence similarity between the mouse and human homologues, indicates an evolutionary conserved function. Upon ligand stimulation, the receptor mobilized intracellular calcium in both a recombinant system as well as in human granulocytes. We found the human gene to be predominantly expressed in peripheral blood leukocytes and, to a lesser extent, in spleen. We suggest the designation FFA(2)R to this second receptor activated by free fatty acids. The first-described FFAR, now named FFA(1)R, is activated by medium- to long-chain free fatty acids.
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SCFAs can activate several G-protein coupled receptors, of which free fatty acid receptor 2 (FFAR2) and 3 (FFAR3) are the most investigated.
“SCFAs can activate several G-protein coupled receptors (GPCR), of which free fatty acid receptor 2 (FFAR2, also referred to as GPR43) and 3 (FFAR3, also referred to as GPR41) are the most investigated (Brown et al., 2003;Le Poul et al., 2003;Nilsson et al., 2003).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Nilsson et al., 2003
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- Authors
- Nilsson, N. E., Kotarsky, K., Owman, C., & Olde, B.
- Affiliations
- Lund University (SE)
- Corresponding author
- Nilsson, Niclas E
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2003-04
- Volume
- 303
- Issue
- 4
- Pages
- 1047-1052
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1972691065
- Cited by
- 540
- References
- 1
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 30 · 2023: 35 · 2022: 25 · 2021: 41 · 2020: 32 · 2019: 22 · 2018: 29 · 2017: 20 · 2016: 42 · 2015: 23 · 2014: 25 · 2013: 39 · 2012: 23
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- FFAR2, GPR43, short-chain fatty acids, leukocytes, granulocytes, calcium mobilization, acetate, propionate, butyrate, G protein-coupled receptors, receptor cloning, ligand specificity, evolutionary conservation, immune regulation
- MeSH terms
- Amino Acid Sequence, Animals, Calcium, Dose-Response Relationship, Drug, Fatty Acids, Volatile, Humans, Leukocytes, Ligands, Molecular Sequence Data, Receptors, Cell Surface, RNA, Messenger, Tissue Distribution, Sequence Homology, Amino Acid, Receptors, G-Protein-Coupled, Mice, Rats
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