The opposing effects of n-3 and n-6 fatty acids.
Polyunsaturated fatty acids (PUFAs) can be classified in n-3 fatty acids and n-6 fatty acids, and in westernized diet the predominant dietary PUFAs are n-6 fatty acids. Both types of fatty acids are precursors of signaling molecules with opposing effects, that modulate membrane microdomain composition, receptor signaling and gene expression. The predominant n-6 fatty acid is arachidonic acid, which is converted to prostaglandins, leukotrienes and other lipoxygenase or cyclooxygenase products. These products are important regulators of cellular functions with inflammatory, atherogenic and prothrombotic effects. Typical n-3 fatty acids are docosahexaenoic acid and eicosapentaenoic acid, which are competitive substrates for the enzymes and products of arachidonic acid metabolism. Docosahexaenoic acid- and eicosapentaenoic acid-derived eicosanoids antagonize the pro-inflammatory effects of n-6 fatty acids. n-3 and n-6 fatty acids are ligands/modulators for the nuclear receptors NFkappaB, PPAR and SREBP-1c, which control various genes of inflammatory signaling and lipid metabolism. n-3 Fatty acids down-regulate inflammatory genes and lipid synthesis, and stimulate fatty acid degradation. In addition, the n-3/n-6 PUFA content of cell and organelle membranes, as well as membrane microdomains strongly influences membrane function and numerous cellular processes such as cell death and survival.
Schmitz
Gerd
G
Institute of Clinical Chemistry, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. gerd.schmitz@klinik.uni-regensburg.de
Ecker
Josef
J
D000818:Animals; D015777:Eicosanoids / Q000096:biosynthesis; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000502:physiology*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008560:Membrane Fluidity / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology
D015777:Eicosanoids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D016328:NF-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled