ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Novel identification of the free fatty acid receptor FFAR1 that promotes contraction in airway smooth muscle.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- The role of fatty acid metabolism in acute lung injury: a special focus on immunometabolism.Cellular and molecular life sciences : CMLS · 2024Pooled it
- Activation of G protein-coupled receptor 40 alleviates STAT6 activation, airway inflammation and mucus hypersecretion in allergic asthma.Current research in pharmacology and drug discovery · 2026Article
- Effect of plasma free fatty acids on lung function in male COPD patients.Scientific reports · 2025Article
- Bronchomotor tone imbalance evokes airway hyperresponsiveness.Expert review of respiratory medicine · 2024Review
- A clinician's guide to effects of obesity on childhood asthma and into adulthood.Expert review of respiratory medicine · 2024Review
- GPR40/GPR120 Agonist GW9508 Improves Metabolic Syndrome-Exacerbated Periodontitis in Mice.International journal of molecular sciences · 2024Article
- Impact of obesity on airway remodeling in asthma: pathophysiological insights and clinical implications.Frontiers in allergy · 2024Review
- The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma.FEMS microbes · 2024Article
- Mechanistic Links Between Obesity and Airway Pathobiology Inform Therapies for Obesity-Related Asthma.Paediatric drugs · 2023Review
- Targeting of G-protein coupled receptor 40 alleviates airway hyperresponsiveness through RhoA/ROCK1 signaling pathway in obese asthmatic mice.Respiratory research · 2023Article
- Metabolic Contributions to Pathobiology of Asthma.Metabolites · 2023Review
- The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma.bioRxiv : the preprint server for biology · 2023Article
- Melatonin MTAmerican journal of physiology. Lung cellular and molecular physiology · 2021Article
- Plasma lipid biomarkers in relation to BMI, lung function, and airway inflammation in pediatric asthma.Metabolomics : Official journal of the Metabolomic Society · 2021Article
- FFAR1 activation attenuates histamine-induced myosin light chain phosphorylation and cortical tension development in human airway smooth muscle cells.Respiratory research · 2020Article
- Free Fatty Acid Receptor 1 Signaling Contributes to Migration, MMP-9 Activity, and Expression of IL-8 Induced by Linoleic Acid in HaCaT Cells.Frontiers in pharmacology · 2020Article
- Obesity-induced asthma: Role of free fatty acid receptors.The Japanese dental science review · 2019Review
- Dietary Acid Load: A Novel Nutritional Target in Overweight/Obese Children with Asthma?Nutrients · 2019Article
- Pharmacological stimulation of G-protein coupled receptor 40 alleviates cytokine-induced epithelial barrier disruption in airway epithelial Calu-3 cells.International immunopharmacology · 2019Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Obesity is one of the major risk factors for asthma. Previous studies have demonstrated that free fatty acid levels are elevated in the plasma of obese individuals. Medium- and long-chain free fatty acids act as endogenous ligands for the free fatty acid receptors FFAR1/GPR40 and FFAR4/GPR120, which couple to Gq proteins. We investigated whether FFAR1 and FFAR4 are expressed on airway smooth muscle and whether they activate Gq-coupled signaling and modulate airway smooth muscle tone. We detected the protein expression of FFAR1 and FFAR4 in freshly dissected native human and guinea pig airway smooth muscle and cultured human airway smooth muscle (HASM) cells by immunoblotting and immunohistochemistry. The long-chain free fatty acids (oleic acid and linoleic acid) and GW9508 (FFAR1/FFAR4 dual agonist) dose-dependently stimulated transient intracellular Ca(2+) concentration ([Ca(2+)]i) increases and inositol phosphate synthesis in HASM cells. Downregulation of FFAR1 or FFAR4 in HASM cells by small interfering RNA led to a significant inhibition of the long-chain free fatty acids-induced transient [Ca(2+)]i increases. Oleic acid, linoleic acid, or GW9508 stimulated stress fiber formation in HASM cells, potentiated acetylcholine-contracted guinea pig tracheal rings, and attenuated the relaxant effect of isoproterenol after an acetylcholine-induced contraction. In contrast, TUG-891 (FFAR4 agonist) did not induce the stress fiber formation or potentiate acetylcholine-induced contraction. These results suggest that FFAR1 is the functionally dominant free fatty acid receptor in both human and guinea pig airway smooth muscle. The free fatty acid sensors expressed on airway smooth muscle could be an important modulator of airway smooth muscle tone.
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