The Dual Role of Free Fatty Acid Signaling in Inflammation and Therapeutics
Caroline M.O. Volpe,
Jose A. Nogueira-Machado.
Obesity, type 2 diabetes, insulin resistance, dyslipidemia, cardiovascular diseases and atherosclerosis have all
been associated with high levels of free fatty acid (FFA). In the present review, we suggest that FFA may act as either
pro- or anti-inflammatory agents depending on the chemical structure. Saturated fatty acids (SFA) and polyunsaturated
fatty acids (PUFA) significantly differ in their contributions to inflammation. While SFAs have been shown to induce inflammation,
PUFAs have anti-inflammatory effects by downregulating NF-kappaB, IL-1β, TNFα- and IL-6 despite
upregulating of IL-10. It is suggested that FFA may activate Toll Like Receptor-4 (TLR4) and G protein-coupled receptors
(GPCR) activating signaling pathways that promote production and release of inflammatory cytokines (IL-6 and
TFN-α). Fatty acid action on TLR4, peroxisome proliferator-activated receptors (PPARs) and GPCRs are potential therapeutic
targets for controlling FFA-induced inflammation. Approaches that downregulate the inflammatory properties of
free fatty acid are discussed in this manuscript. In this review, some patents associated with controlling FFA effects are
Keywords: Free fatty acid (FFA), GPCR (G-protein-coupled receptors), inflammation, PPAR (peroxisome proliferatoractivated
receptors), Toll-like receptors (TLR).
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