ArticleBiochemical pharmacology2017
Free-fatty acid receptor-4 (FFA4) modulates ROS generation and COX-2 expression via the C-terminal β-arrestin phosphosensor in Raw 264.7 macrophages.
Article in Biochemical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- The roles of free-fatty acid receptors in the pathophysiology of renal disorders.The Journal of pharmacology and experimental therapeutics · 2026Review
- Type 2 Diabetes and the Lung - Cause and Consequence.Current diabetes reports · 2026Review
- Agonism of FFA4/GPR120 activates tyrosine hydroxylase and confers neuroprotection from 6-OHDA-induced cytotoxicity in PC12 cells and in a rat 6-OHDA model of Parkinson's disease.Biochemical pharmacology · 2026Article
- Bridging the gut and mind: a narrative review of depression in Crohn's disease and emerging gut-brain axis therapies.Frontiers in neuroscience · 2026Review
- Biased agonism at free-fatty acid receptor-4 (FFA4/GPR120).Pharmacology & therapeutics · 2025Review
- Effect of plasma free fatty acids on lung function in male COPD patients.Scientific reports · 2025Article
- Psilocin, the Psychoactive Metabolite of Psilocybin, Modulates Select Neuroimmune Functions of Microglial Cells in a 5-HTMolecules (Basel, Switzerland) · 2024Article
- Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue.Life (Basel, Switzerland) · 2023Article
- Agonists and hydrogen peroxide mediate hyperoxidation of β2-adrenergic receptor in airway epithelial cells: Implications for tachyphylaxis to β2-agonists in constrictive airway disorders.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Recent Advance in Regulatory Effect of GRP120 on Bone Metabolism.Aging and disease · 2023Review
- Anti-Inflammatory Effects of Serotonin Receptor and Transient Receptor Potential Channel Ligands in Human Small Intestinal Epithelial Cells.Current issues in molecular biology · 2023Article
- Free-fatty acid receptor-1 (FFA1/GPR40) promotes papillary RCC proliferation and tumor growth via Src/PI3K/AKT/NF-κB but suppresses migration by inhibition of EGFR, ERK1/2, STAT3 and EMT.Cancer cell international · 2023Article
- Signaling through Free Fatty Acid Receptor 4 Attenuates Cardiometabolic Disease.Physiology (Bethesda, Md.) · 2022Review
- GPR120 Inhibits RANKL-Induced Osteoclast Formation and Resorption by Attenuating Reactive Oxygen Species Production in RAW264.7 Murine Macrophages.International journal of molecular sciences · 2021Article
- Article
- Carboxy-Terminal Phosphoregulation of the Long Splice Isoform of Free-Fatty Acid Receptor-4 MediatesMolecular pharmacology · 2020Article
- Docosahexaenoic acid protects motor function and increases dopamine synthesis in a rat model of Parkinson's disease via mechanisms associated with increased protein kinase activity in the striatum.Neuropharmacology · 2020Article
- Article
- The adrenergic receptor antagonist carvedilol interacts with serotonin 2A receptors both in vitro and in vivo.Pharmacology, biochemistry, and behavior · 2019Article
- Omega-3 Fatty Acids as Druggable Therapeutics for Neurodegenerative Disorders.CNS & neurological disorders drug targets · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Agonism of the G protein-coupled free-fatty acid receptor-4 (FFA4) has been shown to promote numerous anti-inflammatory effects in macrophages that arise due to interaction with β-arrestin partner proteins. Humans express functionally distinct short and long FFA4 splice variants, such that FFA4-S signals through Gαq/11 and β-arrestin, while FFA4-L is intrinsically biased solely towards β-arrestin signaling. Recently, we and others have shown that phosphorylation of the FFA4 C-terminal tail is responsible for β-arrestin interactability and signaling. Given the significance of β-arrestin in the anti-inflammatory function of FFA4, the goal of this study was to examine the role of the C-terminal β-arrestin phosphosensor in FFA4 signaling induced by PMA and LPS in murine Raw 264.7 macrophages. Our data reveal for the first time that both FFA4 isoforms modulate PMA-induced ROS generation, and that abolishment of the FFA4-S, but not FFA4-L C-terminal phosphosensor, is detrimental to this effect. Furthermore, we show that while both isoforms reduce PMA-induced expression of COX-2, removal of the FFA4-S phosphosensor significantly decreases this response, suggesting that these effects of FFA4-S are β-arrestin mediated. On the contrary, FFA4-S, as well as the truncated C-terminal congener lacking the β-arrestin phosphosensor were both able to reduce LPS-induced NF-κB activity and ERK1/2 phosphorylation. However, FFA4-L and its corresponding mutant were incapable of modulating either, suggesting that these responses are mediated by G protein coupling. Taken together, our data reveal important structure-function and signaling differences between the two FFA4 isoforms, and for the first time link FFA4 to modulation of ROS in macrophages.
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Registered trials
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