Free Fatty Acid Receptors as New Potential Targets in Colorectal Cancer

2020 ◽  
Vol 21 (14) ◽  
pp. 1397-1404
Author(s):  
Adrian Bartoszek ◽  
Jakub Fichna ◽  
Aleksandra Tarasiuk ◽  
Agata Binienda ◽  
Adam Fabisiak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Current Knowledge ◽  
Developed Countries ◽  
Future Directions ◽  
Screening Programs ◽  
Pharmacological Targets ◽  
The Family ◽  
Free Fatty Acid Receptors

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.

scholarly journals Free Fatty acids receptors (FFAR2 and FFAR3) control cell proliferation by regulating cellular glucose uptake

2019 ◽  
Author(s):  
Mohammad Aziz ◽  
Saeed Al Mahri ◽  
Amal Alghamdi ◽  
Maaged AlAkiel ◽  
Monira Al Aujan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Cell Proliferation ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Free Fatty Acids ◽  
Glucose Uptake ◽  
Microarray Data ◽  
Free Fatty Acid Receptors

Abstract Background Colorectal cancer is a worldwide problem which has been associated with changes in diet and lifestyle pattern. As a result of colonic fermentation of dietary fibres, short chain free fatty acids are generated which activate Free Fatty Acid Receptors 2 and 3 (FFAR2 and FFAR3). FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells. Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis. Methods Transcriptome analysis console was used to analyse microarray data from patients and cell lines. We employed shRNA mediated down regulation of FFAR2 and FFAR3 genes which was assessed using qRT-PCR. Assays for glucose uptake and cAMP generation was done along with immunofluorescence studies. For measuring cell proliferation, we employed real time electrical impedance based assay available from xCelligence. Results Microarray data analysis of colorectal cancer patient samples showed a significant down regulation of FFAR2 gene expression. This prompted us to study the FFAR2 in colorectal cancer. Since, FFAR3 shares significant structural and functional homology with FFAR2, we knocked down both these receptors in colorectal cancer cell line HCT 116. These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of GLUT1. Since, FFAR2 and FFAR3 signal through G protein subunit (Gαi), knockdown of these receptors was associated with increased cAMP. Inhibition of PKA did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway. Conclusion: Our results suggest role of FFAR2/FFAR3 genes in increased proliferation of colon cancer cells via enhanced glucose uptake and exclude the role of protein kinase A mediated cAMP signalling. Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes. This study paves the way to understand the mechanism of action of short chain free fatty acid receptors in colorectal cancer.

Abstract 5299: Role of short chain free fatty acid receptors in colorectal cancer

2019 ◽  
Author(s):  
Amal AlGhamdi ◽  
Saeed AlMahri ◽  
Maaged AlAkiel ◽  
Sameer Mohammad ◽  
Mohammad Aziz
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Short Chain ◽  
Free Fatty Acid Receptors

Abstract 5299: Role of short chain free fatty acid receptors in colorectal cancer

2019 ◽  
Author(s):  
Amal AlGhamdi ◽  
Saeed AlMahri ◽  
Maaged AlAkiel ◽  
Sameer Mohammad ◽  
Mohammad Aziz
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Short Chain ◽  
Free Fatty Acid Receptors

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

2019 ◽  
Vol 71 (4) ◽  
pp. 551-555 ◽  
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

Mo1165 Eicosapentaenoic Acid-Free Fatty Acid Strongly Prevents and Suppresses Colonic Tumors in Colitis-Associated Colorectal Cancer

2013 ◽  
Vol 144 (5) ◽  
pp. S-596
Author(s):  
Giulia Piazzi ◽  
Giuseppe D'Argenio ◽  
Vincenzo Lembo ◽  
Giovanna Mazzone ◽  
Anna Prossomariti ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Eicosapentaenoic Acid

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

2016 ◽  
Vol 342 (2) ◽  
pp. 193-199 ◽  
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

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

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.

scholarly journals Structure‐activity relationships of free fatty acid receptors GPR40 and GPR120 agonists based on a docking simulation

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Takafumi Hara ◽  
Akira Hirasawa ◽  
Masato Takeuchi ◽  
Kumiko Ayukawa ◽  
Ryohei Shirai ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Docking Simulation ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Free Fatty Acid Receptors

Characterization of free fatty acid receptors expression in an obesity rat model with high sucrose diet

2018 ◽  
Vol 38 (1) ◽  
pp. 76-82
Author(s):  
Fabián Meza-Cuenca ◽  
J. M. L. Medina-Contreras ◽  
Patrick Mailloux-Salinas ◽  
Luis A. Bautista-Hernández ◽  
Beatríz Buentello-Volante ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Rat Model ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
Free Fatty Acid Receptors ◽  
High Sucrose
Sign in / Sign up

Export Citation Format

Share Document