Signaling through Free Fatty Acid Receptor 4 Attenuates Cardiometabolic Disease

Timothy D. O’connell, Katie Murphy, Naixin Zhang, Sara J. Puccini, Chastity L Healy, Brian A. Harsch, Michael J. Zhang, Gregory C. Shearer

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


A surge in the prevalence of obesity and metabolic syndrome, which promote systemic inflammation, underlies an increase in cardiometabolic disease. Free fatty acid receptor 4 is a nutrient sensor for long-chain fatty acids, like ω3-poly-unsaturated fatty acids (ω3-PUFAs), that attenuates metabolic disease and resolves inflammation. Clinical trials indicate ω3-PUFAs are cardioprotective, and this review discusses the mechanistic links between ω3-PUFAs, free fatty acid receptor 4, and attenuation of cardiometabolic disease.

Original languageEnglish (US)
Pages (from-to)311-322
Number of pages12
Issue number6
StatePublished - Nov 2022

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) Grants 1R01HL130099 (to T.D.O. and G.C.S.) and 1R01HL152215 (to T.D.O. and G.C.S.), Minnesota Obesity Prevention Training Program T32 NIH Grant 1T32DK083250-01A1 (to K.A.M.), and NIH Post-doctoral Fellowship F32HL152523 (to M.Z.).

Publisher Copyright:
© 2022 Int. Union Physiol. Sci./Am. Physiol. Soc.


  • 18-hydroxyeico-sapentaenoic acid (18-HEPE)
  • cardiometabolic disease
  • free fatty acid receptor 4 (Ffar4)
  • heart
  • speci-alized proresolving mediators (SPM)
  • ω3-polyunsaturated fatty acids (ω3-PUFAs)

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, N.I.H., Extramural


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