Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

Colorectal cancer (CRC) is one of the most common cancers worldwide. In developed countries, its mortality remains high, yet the prevalence has established owing to effective screening programs; however due to the westernization of lifestyle, the incidences in many other countries have increased. Although the treatment of CRC has improved in the last few years, the side effects of these approaches cannot be neglected. Recently, members of the family of free fatty acid receptors (FFARs) have become attractive pharmacological targets in many diseases, including asthma; studies also point to their role in carcinogenesis. Here, we discuss current knowledge and future directions in FFAR research related to CRC. Contradictory results of FFARs modulation may derive from the pleiotropic effects of FFAR ligands, receptor distribution and different signal transduction. Hence, we indicate directions of further studies to fully use the potential of FFARs in CRC.

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Short-chain free-fatty acid G protein-coupled receptors in colon cancer

Biochemical Pharmacology ◽

10.1016/j.bcp.2021.114483 ◽

2021 ◽

Vol 186 ◽

pp. 114483

Author(s):

Nader H. Moniri ◽

Qadan Farah

Keyword(s):

Colon Cancer ◽

Fatty Acid ◽

Free Fatty Acid ◽

G Protein ◽

G Protein Coupled Receptors ◽

Short Chain ◽

G Protein Coupled

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Anti-atherosclerotic action of GW9508 – Free fatty acid receptors activator – In apoE-knockout mice

Pharmacological Reports ◽

10.1016/j.pharep.2019.02.014 ◽

2019 ◽

Vol 71 (4) ◽

pp. 551-555 ◽

Cited By ~ 1

Author(s):

Maciej Suski ◽

Anna Kiepura ◽

Anna Wiśniewska ◽

Katarzyna Kuś ◽

Anna Skałkowska ◽

...

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Knockout Mice ◽

Apoe Knockout Mice ◽

Free Fatty Acid Receptors

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Diverse effects of G-protein-coupled free fatty acid receptors on the regulation of cellular functions in lung cancer cells

Experimental Cell Research ◽

10.1016/j.yexcr.2016.03.008 ◽

2016 ◽

Vol 342 (2) ◽

pp. 193-199 ◽

Cited By ~ 18

Author(s):

Tsubasa Kita ◽

Yui Kadochi ◽

Kaede Takahashi ◽

Kaori Fukushima ◽

Eri Yamasaki ◽

...

Keyword(s):

Lung Cancer ◽

Fatty Acid ◽

Free Fatty Acid ◽

Cancer Cells ◽

G Protein ◽

Lung Cancer Cells ◽

Cellular Functions ◽

Free Fatty Acid Receptors ◽

G Protein Coupled

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The long-chain fatty acid receptors FFA1 and FFA4 are involved in food intake regulation in fish brain

Journal of Experimental Biology ◽

10.1242/jeb.227330 ◽

2020 ◽

Vol 223 (17) ◽

pp. jeb227330

Author(s):

Cristina Velasco ◽

Marta Conde-Sieira ◽

Sara Comesaña ◽

Mauro Chivite ◽

Adrián Díaz-Rúa ◽

...

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Food Intake ◽

Mrna Abundance ◽

Fish Brain ◽

Protein Levels ◽

Food Intake Regulation ◽

Free Fatty Acid Receptors ◽

Intake Regulation ◽

Long Chain

ABSTRACTWe hypothesized that the free fatty acid receptors FFA1 and FFA4 might be involved in the anorectic response observed in fish after rising levels of long-chain fatty acids (LCFAs) such as oleate. In one experiment we demonstrated that intracerebroventricular (i.c.v.) treatment of rainbow trout with FFA1 and FFA4 agonists elicited an anorectic response 2, 6 and 24 h after treatment. In a second experiment, the same i.c.v. treatment resulted after 2 h in an enhancement in the mRNA abundance of anorexigenic neuropeptides pomca1 and cartpt and a decrease in the values of orexigenic peptides npy and agrp1. These changes occurred in parallel with those observed in the mRNA abundance and/or protein levels of the transcription factors Creb, Bsx and FoxO1, protein levels and phosphorylation status of Ampkα and Akt, and mRNA abundance of plcb1 and itrp3. Finally, we assessed in a third experiment the response of all these parameters after 2 h of i.c.v. treatment with oleate (the endogenous ligand of both free fatty acid receptors) alone or in the presence of FFA1 and FFA4 antagonists. Most effects of oleate disappeared in the presence of FFA1 and FFA4 antagonists. The evidence obtained supports the involvement of FFA1 and FFA4 in fatty acid sensing in fish brain, and thus involvement in food intake regulation through mechanisms not exactly comparable (differential response of neuropeptides and cellular signalling) to those known in mammals.

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