title: The dual role of free fatty acid signaling in inflammation and therapeutics.
abstract: 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, TNF-α 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.
authors.affiliation: Núcleo de Pós-Graduação e Pesquisa (NPGP), Hospital Santa Casa de Misericórdia de Belo Horizonte, Belo Horizonte, MG, Brazil. aunog.bh@terra.com.br.
authors.forename: Caroline M O
authors.initials: CM
authors.lastname: Volpe
authors.forename: José A
authors.initials: JA
authors.lastname: Nogueira-Machado
mesh_terms: D000818:Animals; D004358:Drug Therapy; D005230:Fatty Acids, Nonesterified / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D010330:Patents as Topic; D047492:Peroxisome Proliferator-Activated Receptors / Q000187:drug effects; D020025:Peroxisome Proliferators / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D047492:Peroxisome Proliferator-Activated Receptors; D020025:Peroxisome Proliferators; D043562:Receptors, G-Protein-Coupled; D051197:Toll-Like Receptor 4