The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets
Open accessAbstract
The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors free fatty acid receptor 2 (FFA2) and FFA3 are activated by these SCFAs, and several lines of evidence indicate that FFA2 and FFA3 mediate beneficial effects associated with a fiber-rich diet, and that they may be of interest as targets for treatment of inflammatory and metabolic diseases. FFA2 is highly expressed on immune cells, in particular neutrophils, and several studies suggest that the receptor plays a role in diseases involving a dysfunctional neutrophil response, such as inflammatory bowel disease (IBD). Both FFA2 and FFA3 have been implicated in metabolic diseases such as type 2 diabetes and in regulation of appetite. More research is however required to clarify the potential of the receptors as drug targets and establish if activation or inhibition would be the preferred mode of action. The availability of potent and selective receptor modulators is a prerequisite for these studies. The few modulators of FFA2 or FFA3 that have been published hitherto in the peer-reviewed literature in general have properties that make them less than ideal as such tools, but published patent applications indicate that better tool compounds might soon become available which should enable studies critical to validate the receptors as new drug targets.
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Citations
Cites
Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
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Human nutrition, the gut microbiome and the immune system
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Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40
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“A high intake of fiber is associated with decreased risk of and beneficial effects on the IBDs ulcerative colitis and Crohn’s disease (Hou et al., 2011).”
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Cited by
den Besten, G., van Eunen, K., Groen, A. K., Venema, K., Reijngoud, D.-J., & Bakker, B. M. (2013) · Journal of Lipid Research · doi:10.1194/jlr.r036012 · Cited by 5,048
Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism
Morrison, D. J., & Preston, T. (2016) · Gut Microbes · doi:10.1080/19490976.2015.1134082 · Cited by 3,781
Gut Microbiota Metabolism of Dietary Fiber Influences Allergic Airway Disease and Hematopoiesis
Trompette, A., Gollwitzer, E. S., Yadava, K., Sichelstiel, A. K., Sprenger, N., Ngom-Bru, C., Blanchard, C., Junt, T., Nicod, L. P., Harris, N. L., et al. (2014) · Nature Medicine · doi:10.1038/nm.3444 · Cited by 2,862
The role of the gut microbiota in NAFLD
Leung, C., Rivera, L., Furness, J. B., & Angus, P. W. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.85 · Cited by 1,020
Free Fatty Acid Receptors in Health and Disease
Kimura, I., Ichimura, A., Ohue-Kitano, R., & Igarashi, M. (2020) · Physiological Reviews · doi:10.1152/physrev.00041.2018 · Cited by 1,018
Metadata
- Authors
- Ulven, T.
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2012
- Volume
- 3
- Pages
- 111-111
- ISSN
- 1664-2392 (ISSN-L)
- OpenAlex
- W2069247721
- Cited by
- 271
- References
- 10
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- gold
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- Ulven, T. (2012). Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets. Frontiers in Endocrinology. https://doi.org/10.3389/fendo.2012.00111
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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