Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Feb 21;11(4):750.
doi: 10.3390/cells11040750.

Free Fatty Acid Receptors (FFARs) in Adipose: Physiological Role and Therapeutic Outlook

Saeed Al Mahri  1 , Shuja Shafi Malik  1 , Maria Al Ibrahim  1 , Esraa Haji  1 , Ghida Dairi  1   2   3 , Sameer Mohammad  1
Affiliations
Review

Free Fatty Acid Receptors (FFARs) in Adipose: Physiological Role and Therapeutic Outlook

Saeed Al Mahri et al. Cells. .

Abstract

Fatty acids (FFAs) are important biological molecules that serve as a major energy source and are key components of biological membranes. In addition, FFAs play important roles in metabolic regulation and contribute to the development and progression of metabolic disorders like diabetes. Recent studies have shown that FFAs can act as important ligands of G-protein-coupled receptors (GPCRs) on the surface of cells and impact key physiological processes. Free fatty acid-activated receptors include FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41), and FFAR4 (GPR120). FFAR2 and FFAR3 are activated by short-chain fatty acids like acetate, propionate, and butyrate, whereas FFAR1 and FFAR4 are activated by medium- and long-chain fatty acids like palmitate, oleate, linoleate, and others. FFARs have attracted considerable attention over the last few years and have become attractive pharmacological targets in the treatment of type 2 diabetes and metabolic syndrome. Several lines of evidence point to their importance in the regulation of whole-body metabolic homeostasis including adipose metabolism. Here, we summarize our current understanding of the physiological functions of FFAR isoforms in adipose biology and explore the prospect of FFAR-based therapies to treat patients with obesity and Type 2 diabetes.

Keywords: G-protein-coupled receptors; adipogenesis; adipose tissue; free fatty acid receptors; thermogenesis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Ligand specificity of free fatty acid receptors. FFAR1 and FFAR4 act as receptors for long chain fatty acids (LCFAs), whereas short chain fatty acids (SCFAs) selectively activate FFAR2 and FFAR3.
Figure 2
Figure 2
Physiological significance of FFAR4 in adipose tissue metabolism. Evidence from human, mouse, and in vitro studies.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wang L., Zhu L., Meister J., Bone D.B., Pydi S.P., Rossi M., Wess J. Use of DREADD Technology to Identify Novel Targets for Antidiabetic Drugs. Annu. Rev. Pharmacol. Toxicol. 2021;61:421–440. doi: 10.1146/annurev-pharmtox-030220-121042. - DOI - PubMed
    1. Thompson M.D., Siminovitch K.A., Cole D.E.C. G Protein-Coupled Receptor Pharmacogenetics. Pharm. Drug Discov. Dev. 2008;448:139–185. doi: 10.1007/978-1-59745-205-2_8. - DOI - PubMed
    1. Krishna S., Insel P. GPCRs as targets for approved drugs: How many targets and how many drugs? Mol. Pharmacol. 2018;93:251–258. - PMC - PubMed
    1. Hauser A.S., Attwood M.M., Rask-Andersen M., Schiöth H.B., Gloriam D.E. Trends in GPCR drug discovery: New agents, targets and indications. Nat. Rev. Drug Discov. 2017;16:829–842. doi: 10.1038/nrd.2017.178. - DOI - PMC - PubMed
    1. Fredriksson R., Lagerström M.C., Lundin L.G., Schiöth H.B. The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol. 2003;63:1256–1272. doi: 10.1124/mol.63.6.1256. - DOI - PubMed

Publication types