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Review
. 2021 Apr 24;9(5):467.
doi: 10.3390/biomedicines9050467.

Anti-Atherosclerotic Potential of Free Fatty Acid Receptor 4 (FFAR4)

Anna Kiepura  1 , Kamila Stachyra  1 , Rafał Olszanecki  1
Affiliations
Review

Anti-Atherosclerotic Potential of Free Fatty Acid Receptor 4 (FFAR4)

Anna Kiepura et al. Biomedicines. .

Abstract

Fatty acids (FAs) are considered not only as a basic nutrient, but are also recognized as signaling molecules acting on various types of receptors. The receptors activated by FAs include the family of rhodopsin-like receptors: GPR40 (FFAR1), GPR41 (FFAR3), GPR43 (FFAR2), GPR120 (FFAR4), and several other, less characterized G-protein coupled receptors (GPR84, GPR109A, GPR170, GPR31, GPR132, GPR119, and Olfr78). The ubiquitously distributed FFAR4 can be activated by saturated and unsaturated medium- and long-chain fatty acids (MCFAs and LCFAs), as well as by several synthetic agonists (e.g., TUG-891). The stimulation of FFAR4 using selective synthetic agonists proved to be promising strategy of reduction of inflammatory reactions in various tissues. In this paper, we summarize the evidence showing the mechanisms of the potential beneficial effects of FFAR4 stimulation in atherosclerosis. Based partly on our own results, we also suggest that an important mechanism of such activity may be the modulatory influence of FFAR4 on the phenotype of macrophage involved in atherogenesis.

Keywords: FFAR4; apoE-knockout mice; atherosclerosis; free fatty acid receptors; inflammation; liver steatosis; macrophages.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Anti-atherosclerotic activity of TUG-891 in apoE-/- mice. (a): The Representative micrographs showing the areas of Oil Red O–stained lesions in control and TUG-891-treated groups (preliminary data of n = 5 per group). (b): M1/M2 marker expression in bone marrow derived macrophages (BMDM). BMDMs were pre-treated with either 10µM AH-7614 and 10µM TUG-891 for 1 h and then treated with 100 ng/mL LPS + 20 ng/mL INF-γ or 20 ng/mL IL-4 for 24 h and then used in quantitative RT-PCR analyses. (* p  <  0.05, ** p < 0.01, **** p  <  0.0001 as determined by 1-way ANOVA with Tukey’s post-test; n = 3–4 per group; unpublished data).
Figure 2
Figure 2
Diagram showing the potential cellular and molecular mechanisms of anti-atherosclerotic actions of FFAR4 within the vessel wall. Potential indirect action of FFAR4 stimulation on atherosclerosis via inhibition of steatosis and steatohepatitis is detailed in the text.
See this image and copyright information in PMC

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