The Dual Role of Free Fatty Acid Signaling in Inflammation and Therapeutics
Recent Patents on Endocrine Metabolic & Immune Drug Discovery, 7
): 189-197.Author(s): Caroline M.O. Volpe
and Jose A Nogueira-Machado
Núcleo de Pós-Graduação e Pesquisa (NPGP), Hospital Santa Casa de Misericórdia de Belo Horizonte, Belo Horizonte, MG, Brazil.
AbstractObesity, 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-1 β, 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 also reported.
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