ArticleCardiovascular research2022
Free fatty acid receptor 4 responds to endogenous fatty acids to protect the heart from pressure overload.
Article in Cardiovascular research, 2022. 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.
- Morchella polysaccharide ameliorates myocardial infarction inflammation in mice through increasing gut microbiota-derived 12-HEPE.Acta pharmacologica Sinica · 2026Article
- Oxylipin composition of high-density lipoprotein is altered in men and Hispanic adults with mild cognitive impairment.Journal of lipid research · 2026Article
- Analysis of mortality risk and influencing factors in female patients with young-onset type 2 diabetes.Frontiers in endocrinology · 2026Article
- Association between triglyceride-glucose-body mass index and adverse prognosis in elderly patients with severe heart failure and type 2 diabetes: a retrospective study based on the MIMIC-IV database.Cardiovascular diabetology · 2025Article
- Microbiota in Gut-Heart Axis: Metabolites and Mechanisms in Cardiovascular Disease.Comprehensive physiology · 2025Review
- Sex differences in the central and peripheral omega 3 oxylipin response to acute systemic inflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- A Cell Autonomous Free fatty acid receptor 4 - ChemR23 Signaling Cascade Protects Cardiac Myocytes from Ischemic Injury.bioRxiv : the preprint server for biology · 2025Article
- Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) Ameliorate Heart Failure through Reductions in Oxidative Stress: A Systematic Review and Meta-Analysis.Antioxidants (Basel, Switzerland) · 2024Review
- ABCA1 and apoA-I dependent 12-hydroxyeicosatetraenoic acid efflux regulates macrophage inflammatory signaling.bioRxiv : the preprint server for biology · 2024Article
- Eicosapentaenoic Acid Rescues Cav1.2-L-Type CaInternational journal of molecular sciences · 2024Article
- Eicosapentaenoic acid and Arachidonic acid Protection Against Left Ventricle Pathology: the Multi-Ethnic Study of Atherosclerosis.medRxiv : the preprint server for health sciences · 2024Article
- A Two-Step Transcriptome Analysis of the Human Heart Reveals Broad and Disease-Responsive Expression of Ectopic Olfactory Receptors.International journal of molecular sciences · 2023Article
- Lipid-Sensing Receptor FFAR4 Modulates Pulmonary Epithelial Homeostasis following Immunogenic Exposures Independently of the FFAR4 Ligand Docosahexaenoic Acid (DHA).International journal of molecular sciences · 2023Article
- Apelin receptor inhibition in ischemia-reperfused mouse hearts protected by endogenous n-3 polyunsaturated fatty acids.Frontiers in pharmacology · 2023Article
- Signaling through Free Fatty Acid Receptor 4 Attenuates Cardiometabolic Disease.Physiology (Bethesda, Md.) · 2022Review
- Esterified Oxylipins: Do They Matter?Metabolites · 2022Review
- Comment on "Activation of the Omega-3 Fatty Acid Receptor GPR120 Protects against Focal Cerebral Ischemic Injury by Preventing Inflammation and Apoptosis in Mice".Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- New Progress in the Molecular Regulations and Therapeutic Applications in Cardiac Oxidative Damage Caused by Pressure Overload.Antioxidants (Basel, Switzerland) · 2022Review
- Mitophagy: A Potential Target for Pressure Overload-Induced Cardiac Remodelling.Oxidative medicine and cellular longevity · 2022Review
- Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
Abstract
aimsFree fatty acid receptor 4 (Ffar4) is a G-protein-coupled receptor for endogenous medium-/long-chain fatty acids that attenuates metabolic disease and inflammation. However, the function of Ffar4 in the heart is unclear. Given its putative beneficial role, we hypothesized that Ffar4 would protect the heart from pathologic stress. METHODS AND
resultsIn mice lacking Ffar4 (Ffar4KO), we found that Ffar4 is required for an adaptive response to pressure overload induced by transverse aortic constriction (TAC), identifying a novel cardioprotective function for Ffar4. Following TAC, remodelling was worsened in Ffar4KO hearts, with greater hypertrophy and contractile dysfunction. Transcriptome analysis 3-day post-TAC identified transcriptional deficits in genes associated with cytoplasmic phospholipase A2α signalling and oxylipin synthesis and the reduction of oxidative stress in Ffar4KO myocytes. In cultured adult cardiac myocytes, Ffar4 induced the production of the eicosapentaenoic acid (EPA)-derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Furthermore, the activation of Ffar4 attenuated cardiac myocyte death from oxidative stress, while 18-HEPE rescued Ffar4KO myocytes. Systemically, Ffar4 maintained pro-resolving oxylipins and attenuated autoxidation basally, and increased pro-inflammatory and pro-resolving oxylipins, including 18-HEPE, in high-density lipoproteins post-TAC. In humans, Ffar4 expression decreased in heart failure, while the signalling-deficient Ffar4 R270H polymorphism correlated with eccentric remodelling in a large clinical cohort paralleling changes observed in Ffar4KO mice post-TAC.
conclusionOur data indicate that Ffar4 in cardiac myocytes responds to endogenous fatty acids, reducing oxidative injury, and protecting the heart from pathologic stress, with significant translational implications for targeting Ffar4 in cardiovascular disease.
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