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 Role of the G protein-coupled receptors GPR84 and GPR119 in the central regulation of food intake in rainbow trout

2021 ◽  
Author(s):  
Cristina Velasco ◽  
Marta Conde-Sieira ◽  
Sara Comesaña ◽  
Mauro Chivite ◽  
Jesús M. Míguez ◽  
...  
Keyword(s):  
Rainbow Trout ◽  
Food Intake ◽  
Mrna Abundance ◽  
Signalling Pathways ◽  
Fish Brain ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Food Intake Regulation ◽  
Intake Regulation ◽  
The Impact

We evaluated the role of GPR84 and GPR119 in food intake regulation in fish using rainbow trout (Oncorhynchus mykiss) as a model. In a first experiment, we assessed the effects on food intake of intracerebroventricular treatment with agonists of these receptors. In a second experiment, we assessed in hypothalamus and hindbrain the impact of the same treatments on mRNA abundance of neuropeptides involved in the metabolic control of food intake (npy, agrp1, pomca1, and cartpt) as well as in changes in parameters related to signalling pathways and transcription factors involved in the integrative response leading to neuropeptide production. Treatment with both agonists elicited an anorectic response in rainbow trout attributable to changes observed in the mRNA abundance of the four neuropeptides. Changes in neuropeptides relate to changes observed in mRNA abundance and phosphorylation status of the transcription factor Foxo1. These changes occurred in parallel with changes in phosphorylation status of Ampkα and Akt, mRNA abundance of mTOR as well as in signalling pathways related to PLCβ and IP3. These results allow us to suggest that 1) at least part of the capacity of fish brain to sense MCFA like octanoate depends on the function of GPR84, and 2) the capacity of fish brain to sense NAE or triglyceride-derived molecules through binding of these ligands to GPR119.

scholarly journals Hypothalamic mechanisms linking fatty acid sensing and food intake regulation in rainbow trout

2017 ◽  
Vol 59 (4) ◽  
pp. 377-390 ◽  
Author(s):  
Cristina Velasco ◽  
Cristina Otero-Rodiño ◽  
Sara Comesaña ◽  
Jesús M Míguez ◽  
José L Soengas
Keyword(s):  
Fatty Acids ◽  
Transcription Factors ◽  
Fatty Acid ◽  
Rainbow Trout ◽  
Food Intake ◽  
Food Intake Regulation ◽  
Intake Regulation ◽  
First Time ◽  
Specific Inhibitors ◽  
Fatty Acid Sensing

We assessed in rainbow trout hypothalamus the effects of oleate and octanoate on levels and phosphorylation status of two transcription factors, FoxO1 and CREB, possibly involved in linking activation of fatty acid sensing with modulation of food intake through the expression of brain neuropeptides. Moreover, we assessed changes in the phosphorylation status of three proteins possibly involved in modulation of these transcription factors such as Akt, AMPK and mTOR. In a first experiment, we evaluated, in pools of hypothalamus incubated for 3 h and 6 h at 15°C in a modified Hanks’ medium containing 100 or 500 µM oleate or octanoate, the response of fatty acid sensing, neuropeptide expression and phosphorylation status of proteins of interest. The activation of fatty acid sensing and enhanced anorectic potential occurred in parallel with the activation of Akt and mTOR, and the inhibition of AMPK. The changes in these proteins would relate to a neuropeptide expression through changes in the phosphorylation status of transcription factors under their control, such as CREB and FoxO1, which displayed inhibitory (CREB) or activatory (FoxO1) responses when tissues were incubated with oleate or octanoate. In a second experiment, we incubated hypothalamus for 6 h with 500 µM oleate or octanoate alone or in the presence of specific inhibitors of Akt, AMPK, mTOR, CREB or FoxO1. The presence of inhibitors counteracted the effects of oleate or octanoate on the phosphorylation status of the proteins of interest. The results support, for the first time in fish, the involvement of these proteins in the regulation of food intake by fatty acids.

scholarly journals Effects of CCK-8 and GLP-1 on fatty acid sensing and food intake regulation in trout

2019 ◽  
Vol 62 (3) ◽  
pp. 101-116
Author(s):  
Cristina Velasco ◽  
Sara Comesaña ◽  
Marta Conde-Sieira ◽  
Jesús M Míguez ◽  
José L Soengas
Keyword(s):  
Fatty Acid ◽  
Food Intake ◽  
Metabolic Regulation ◽  
Acid Metabolism ◽  
Sensing Systems ◽  
Food Intake Regulation ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Intake Regulation ◽  
Fatty Acid Sensing

We hypothesize that cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) are involved in the modulation of metabolic regulation of food intake by fatty acids in fish. Therefore, we assessed in rainbow trout (Oncorhynchus mykiss) the effects of intracerebroventricular treatment with 1 ng/g of CCK-8 and with 2 ng/g of GLP-1 on food intake, expression of neuropeptides involved in food intake control and the activity of fatty acid-sensing systems in hypothalamus and hindbrain. Food intake decreased up to 24 h post-treatment to 49.8–72.3% and 3.1–17.8% for CCK-8 and GLP-1, respectively. These anorectic responses are associated with changes in fatty acid metabolism and an activation of fatty acid-sensing mechanisms in the hypothalamus and hindbrain. These changes occurred in parallel with those in the expression of anorexigenic and orexigenic peptides. Moreover, we observed that the activation of fatty acid sensing and the enhanced anorectic potential elicited by CCK-8 and GLP-1 treatments occurred in parallel with the activation of mTOR and FoxO1 and the inhibition of AMPKα, BSX and CREB. The results are discussed in the context of metabolic regulation of food intake in fish.

scholarly journals Free fatty acid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Celia Briscoe ◽  
Andrew Brown ◽  
Nick Holliday ◽  
Stephen Jenkinson ◽  
Graeme Milligan ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
Short Chain Fatty Acids ◽  
Propanoic Acid ◽  
Pentanoic Acid ◽  
Free Fatty Acid Receptors ◽  
Long Chain

Free fatty acid receptors (FFA, nomenclature as agreed by the NC-IUPHAR Subcommittee on free fatty acid receptors [111, 24]) are activated by free fatty acids. Long-chain saturated and unsaturated fatty acids (including C14.0 (myristic acid), C16:0 (palmitic acid), C18:1 (oleic acid), C18:2 (linoleic acid), C18:3, (α-linolenic acid), C20:4 (arachidonic acid), C20:5,n-3 (EPA) and C22:6,n-3 (docosahexaenoic acid)) activate FFA1 [8, 50, 60] and FFA4 receptors [41, 48, 90], while short chain fatty acids (C2 (acetic acid), C3 (propanoic acid), C4 (butyric acid) and C5 (pentanoic acid)) activate FFA2 [9, 62, 86] and FFA3 [9, 62] receptors. The crystal structure for agonist bound FFA1 has been described [108].

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.

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

scholarly journals Signals from intra-abdominal fat modulate insulin and leptin sensitivity through different mechanisms: Neuronal involvement in food-intake regulation

2006 ◽  
Vol 3 (3) ◽  
pp. 223-229 ◽  
Author(s):  
Tetsuya Yamada ◽  
Hideki Katagiri ◽  
Yasushi Ishigaki ◽  
Takehide Ogihara ◽  
Junta Imai ◽  
...  
Keyword(s):  
Food Intake ◽  
Abdominal Fat ◽  
Leptin Sensitivity ◽  
Food Intake Regulation ◽  
Intake Regulation

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
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