A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs
Abstract
Fatty acids, which are essential nutritional components, are also involved in cardiovascular and metabolic diseases. Here we report a human cell surface receptor that we name free fatty acid receptor (FFAR), because it is specifically activated by medium to long-chain free fatty acids. The receptor belongs to the class of seven-transmembrane, G-protein coupled receptors (GPCRs) and also mediates responses to antidiabetic drugs of the thiazolidinedione type. It is expressed in skeletal muscle, heart, liver, and pancreatic beta-cells. Stimulation of FFAR increases the intracellular calcium concentration in cells expressing the receptor in a native (pancreatic beta-cell line) or in a recombinant form. In view of the nature of the activating substances, their physiological role in the body, and the tissue distribution of FFAR we suggest the term "nutrient sensing receptor" for receptors acting at the interface between dietary components and signalling molecules.
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Some effects of NEFA may be secondary to activation of the FFA receptor GPR40 (FFAR1), which is expressed at high levels in both mouse and human β-cells.
“Some of these effects may be secondary to activation of the FFA receptor GPR40 (354) (encoded by FFAR1), which is expressed at high levels in both mouse and human β-cells (Appendix Figures 11E and 12A).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [354]
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- Authors
- Kotarsky, K., Nilsson, N. E., Flodgren, E., Owman, C., & Olde, B.
- Affiliations
- Lund University (SE)
- Corresponding author
- Olde, Björn
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 301
- Issue
- 2
- Pages
- 406-410
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2084862721
- Cited by
- 352
- References
- 0
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 12 · 2020: 12 · 2019: 13 · 2018: 15 · 2017: 14 · 2016: 23 · 2015: 17 · 2014: 16 · 2013: 25 · 2012: 24
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Foundation for Food and Agriculture Research
- Vetenskapsrådet
- 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
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- free fatty acid receptors, G protein-coupled receptors, thiazolidinediones, free fatty acids, intracellular calcium, pancreatic beta cells, skeletal muscle, liver, heart
- MeSH terms
- Rosiglitazone, Aequorin, Animals, Calcium, Cell Line, Dose-Response Relationship, Drug, Fatty Acids, Nonesterified, Humans, Hypoglycemic Agents, Islets of Langerhans, Palmitic Acids, Receptors, Cell Surface, Thiazoles, Time Factors, Tissue Distribution, Genes, Reporter, Thiazolidinediones, Mice
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