Free Fatty Acid GPCR Assays
Background of Free Fatty Acid Receptors
Free fatty acid receptors (FFA receptors) are a family of G protein-coupled receptors also known as the GPR40 family, consisting of FFA1 (GRP40), FFA2 (GRP43), FFA3 (GRP41), and FFA4 (GPR120). Free fatty acids play an important role in metabolism, immune response, and many other physiological processes. Long-chain fatty acids (LCFAs) are generated from dietary intake, adipose recycling, and hepatic fatty acids. Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are derived from the anaerobic bacteria fermentation of dietary polysaccharides and fiber. LCFAs selectively activate FFA1 receptors, whereas SCFAs stimulate signal transduction by activating FFA2 and FFA3 receptors.
Fig.1 Crystal structure of Human GPR40 bound to allosteric agonist TAK-875. (Briscoe, 2019)
Distribution and Function of Free Fatty Acid Receptors
FFA1 receptors are primarily distributed in pancreatic β cells which are responsible for regulating the release of glucose-stimulated insulin. FFA receptors are also located in adipose tissue, brain, different immune cells, and sympathetic ganglia, modulating multiple physiological processes, including inflammation, incretin secretion, obesity, and so on. FAA receptors have been regarded as hopeful targets for the development of new drugs for the treatments of diabetes, obesity, human breast cancer, and so on.
Subtypes and Mechanism of Free Fatty Acid Receptors
The free fatty acid receptors contain FFA1, FFA2, FFA3, and FFA4 receptors. The signal transduction of FFA1 receptors is mediated by Gq/G11 Gs, Gi/Go, and Gαi proteins. FFA2 receptors couple Gq/G11 and Gi/Go proteins. FFA3 receptors promote signal transduction through Gi/Go proteins. And FFA4 receptors couple the family of Gq/G11 proteins.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| FFA1 receptor | FFAR1 |
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| FFA2 receptor | FFAR2 |
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| FFA3 receptor | FFAR3 |
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| FFA4 receptor | FFAR4 |
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Assay List of Free Fatty Acid Receptors
Creative Biolabs can provide a range of assays of free fatty acid receptors. You can choose the assay in the list or contact us for more information:
| Assay No. | Assay Name | Host Cell | Assay Type | Datasheet |
|---|---|---|---|---|
| IP1 Assay | ||||
| S01YF-1122-KX432 | Magic™ Human FFAR1 In Vitro IP1 Assay | CHO-K1 | IP1 Assay | |
Published Data
| Paper Title | Development of free fatty acid receptor 4 (FFA4/GPR120) agonists in health science |
| Journal | Biomolecules & Therapeutics |
| Published | 2021 |
| Abstract | Free fatty acid receptor 4 (FFA4, also known as GPR120) is considered to recognize and bind long-chain polyunsaturated fatty acids such as DHA and EPA, which plays a considerable role in regulating obesity-induced metaflammation and GLP-1 secretion. The study has reviewed the development of FFA4 agonists, including GW9508, NCG21, grifolic acid, TUG-891, GSK137647A, Compound A, Metabolex compounds, TUG-1197, and KDT501, and antagonists, including AH-7614. The study has compared FFA4 agonist activities in an AP-TGF-α shedding assay system. The study also introduced completed and ongoing clinical trials with natural and synthetic FFA4 agonists. |
| Result |
The study tested the available potency of different FFA4 agonists, including Compound A, GW9508, TUG-891, and GSK. The result of the AP-TGF-α shedding assay demonstrated that Compound A and TUG-891 showed the highest potency, followed by GW9508. GSK showed lower potency and efficacy than GW9508. The activities of natural fatty acids DHA and EPA on FFA4 were also tested, showing some activity. The results of completed and ongoing clinical traits may contribute to finding cures for diabetes and obese patients and exploring the mechanisms of action of metabolic and inflammatory diseases.
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Fig.2. Concentration-response curves of FFA4 agonists in an AP-TGF-α shedding assay. (Son, 2021)
References
- Briscoe C.; et al. Free fatty acid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database. IUPHAR/BPS Guide to Pharmacology CITE. 2019, 2019(4).
- Son, S. E.; et al. Development of free fatty acid receptor 4 (FFA4/GPR120) agonists in health science. Biomolecules & Therapeutics. 2021, 29(1): 22.
