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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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FFAR1
free fatty acid receptor 1
Chromosome 19 Β· 19q13.12
NCBI Gene: 2864Ensembl: ENSG00000126266.5HGNC: HGNC:4498UniProt: O14842
83PubMed Papers
20Diseases
3Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
Clinical Trials
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of calcium ion transportbioactive lipid receptor activitynegative regulation of interleukin-1 beta productionresponse to fatty acidtype 2 diabetes mellitusdiabetes mellitusAlzheimer diseaseParkinson disease
✦AI Summary

FFAR1 is a G protein-coupled receptor that recognizes medium and long-chain fatty acids as natural ligands, playing a central role in metabolic and immune regulation 1. Upon ligand binding, FFAR1 undergoes conformational changes that activate Gq and Gi-mediated signaling pathways, increasing intracellular calcium and modulating cellular responses 2. The receptor's primary physiological function involves glucose homeostasis: fatty acid binding to FFAR1 enhances glucose-stimulated insulin secretion in a glucose-dependent manner, avoiding hypoglycemia risk 3. FFAR1 also mediates anti-inflammatory effects of omega-3 polyunsaturated fatty acids by inhibiting NLRP3 inflammasome activation, thereby preventing inflammation-driven metabolic disorders including type 2 diabetes 4. Additionally, FFAR1 regulates lipid and glucose metabolism in metabolically active tissues; in the retina, it suppresses glucose uptake when fatty acids are available, and dysregulation contributes to neovascular age-related macular degeneration 5. Clinically, FFAR1 represents a promising therapeutic target for type 2 diabetes management through agonists that improve glucose control 6. However, development challenges remain, particularly regarding hepatotoxicity associated with some candidate compounds 63.

Sources cited
1
FFAR1 is activated by long-chain saturated and unsaturated fatty acids and regulates metabolism and immune responses
PMID: 31487233
2
Structural basis of FFAR1 activation: ligand binding causes upward movement of helix V and Gi protein coupling
PMID: 39616615
3
FFAR1 agonists stimulate glucose-dependent insulin release without hypoglycemia and represent therapeutic targets for type 2 diabetes
PMID: 37947382
4
FFAR1 (GPR40) mediates omega-3 fatty acid inhibition of NLRP3 inflammasome activation to prevent metabolic disorder in type 2 diabetes
PMID: 23809162
5
FFAR1 suppresses glucose uptake when fatty acids are available; dysregulation contributes to retinal neovascularization in age-related macular degeneration
PMID: 26974308
6
FFAR1 agonists improve glucose control in type 2 diabetes but hepatotoxicity remains a development challenge
PMID: 31771391
Disease Associationsβ“˜20
type 2 diabetes mellitusOpen Targets
0.39Weak
diabetes mellitusOpen Targets
0.38Weak
Alzheimer diseaseOpen Targets
0.26Weak
Parkinson diseaseOpen Targets
0.25Weak
neurodegenerative diseaseOpen Targets
0.25Weak
lysosomal storage diseaseOpen Targets
0.24Weak
multiple sclerosisOpen Targets
0.24Weak
Alstrom syndromeOpen Targets
0.18Weak
MODYOpen Targets
0.08Suggestive
pemphigus foliaceusOpen Targets
0.08Suggestive
asthmaOpen Targets
0.08Suggestive
cystic fibrosisOpen Targets
0.07Suggestive
idiopathic pulmonary fibrosisOpen Targets
0.07Suggestive
exercise-induced hyperinsulinismOpen Targets
0.07Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.07Suggestive
metabolic syndromeOpen Targets
0.06Suggestive
Hepatic steatosisOpen Targets
0.06Suggestive
hyperinsulinemic hypoglycemia, familial, 2Open Targets
0.06Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.06Suggestive
hyperproinsulinemiaOpen Targets
0.06Suggestive
Pathogenic Variants1
NM_005303.3(FFAR1):c.69_70insTTT (p.Asn23_Val24insPhe)Pathogenic
Hypercholesterolemia, familial, 1
β˜†β˜†β˜†β˜†2022β†’ Residue 23
View on ClinVar β†—
Drug Targets3
FASIGLIFAMPhase III
Free fatty acid receptor 1 positive allosteric modulator
type 2 diabetes mellitus
LY2881835Phase I
Free fatty acid receptor 1 agonist
type 2 diabetes mellitus
SETOGEPRAMPhase II/III
Free fatty acid receptor 1 agonist
Alstrom syndrome
Related Genes
GCGProtein interaction96%GIPProtein interaction93%GNA11Protein interaction91%GNAQProtein interaction91%FFAR3Protein interaction84%GPR84Protein interaction83%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
29%
Brain
5%
Lung
1%
Heart
0%
Liver
0%
Gene Interaction Network
Click a node to explore
FFAR1GCGGIPGNA11GNAQFFAR3GPR84
PROTEIN STRUCTURE
Preparing viewer…
PDB5TZR Β· 2.20 Γ… Β· X-ray
View on RCSB β†—
RankingsWhere FFAR1 stands among ~20K protein-coding genes
  • #5,729of 20,598
    Most Researched83
  • #4,950of 5,498
    Most Pathogenic Variants1
Genes detectedFFAR1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Free Fatty Acid Receptors in Health and Disease.
PMID: 31487233
Physiol Rev Β· 2020
1.00
2
Fatty Acid Transport and Signaling: Mechanisms and Physiological Implications.
PMID: 36347219
Annu Rev Physiol Β· 2023
0.90
3
Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation.
PMID: 23809162
Immunity Β· 2013
0.80
4
For Better or Worse: FFAR1 and FFAR4 Signaling in Cancer and Diabetes.
PMID: 27582526
Mol Pharmacol Β· 2016
0.70
5
An updated patent review of GPR40/ FFAR1 modulators (2020 - present).
PMID: 37947382
Expert Opin Ther Pat Β· 2023
0.60