ABSTRACT
Mediators Called Resolvins and Protectins .............................................................. 310 22.5 Omega-3 Fatty Acids Decrease NFκB-Mediated Inammatory Signaling ......................... 311
22.5.1 The NFκB System ................................................................................................... 311 22.5.2 EPA and DHA Inhibit NFκB Activation and Induction of NFκB Targets .............. 311 22.5.3 EPA and DHA May Promote an Anti-Inammatory Interaction between
PPAR-γ and NFκB .................................................................................................... 311 22.5.4 EPA and DHA May Act through a Cell Surface Receptor That Inhibits
NFκB Activation ...................................................................................................... 312 22.6 Effects of EPA and DHA on T Cells .................................................................................... 312 22.7 Omega-3 Fatty Acids as a Therapeutic Option for Chronic Inammation .......................... 312
22.7.1 General Comments ................................................................................................... 312 22.7.2 Rheumatoid Arthritis ................................................................................................ 313
22.7.2.1 Introduction ................................................................................................ 313 22.7.2.2 Omega-3 PUFAs and Animal Models of RA ............................................ 313 22.7.2.3 Trials of ω-3 PUFAs in RA ....................................................................... 313 22.7.2.4 Meta-Analyses of Trials of ω-3 PUFAs in RA .......................................... 314
22.7.3 Inammatory Bowel Diseases .................................................................................. 314 22.7.3.1 Introduction ................................................................................................ 314 22.7.3.2 Omega-3 PUFAs and Animal Models of IBD ........................................... 314 22.7.3.3 Trials of ω-3 PUFAs in IBD ...................................................................... 315 22.7.3.4 Meta-Analyses of Trials of ω-3 PUFAs in RA .......................................... 315
22.8 Conclusions ........................................................................................................................... 315 Take-Home Messages .................................................................................................................... 316 References ...................................................................................................................................... 317
This chapter will consider two families of polyunsaturated fatty acids (PUFAs), the omega-6 (ω-6) family and the omega-3 (ω-3) family. Omega-6 and ω-3 PUFAs each have a characteristic, distinguishing structural feature, separate dietary sources, and distinct biological properties. PUFAs are fatty acids that have two or more double bonds within the fatty acyl hydrocarbon chain. They form a smaller part of the human diet than saturated or monounsaturated fatty acids. The terms “ω-6” and “ω-3” refer to the characteristic, distinguishing structural feature of these fatty acids: the number (i.e., 6 or 3) indicates the carbon atom in the hydrocarbon chain on which the œrst double bond is found if the terminal methyl carbon is deœned as carbon number one. The simplest ω-6 PUFA is linoleic acid, an 18-carbon fatty acid with two double bonds in the hydrocarbon chain, which is described as 18:2ω-6. The simplest ω-3 PUFA is α-linolenic acid, an 18-carbon fatty acid with three double bonds in the hydrocarbon chain, described as 18:3ω-3. Neither linoleic acid nor α-linolenic acid can be synthesized in animals. However, they are synthesized in plants. Furthermore, animals are not able to interconvert ω-6 and ω-3 PUFAs, but plants can do this. In animals, linoleic and α-linolenic acids are able to be converted to other fatty acids (Figure 22.1). During this conversion the position of the methyl-terminal double bond is retained so that linoleic acid is a precursor to other ω-6 PUFAs, and α-linolenic acid is a precursor to other ω-3 PUFAs (Figure 22.1). The conversion of linoleic and α-linolenic acids to these other fatty acids occurs through the insertion of additional double bonds into the hydrocarbon chain in a process called unsaturation and by elongation of the hydrocarbon chain. By this pathway, linoleic acid can be converted to arachidonic acid (20:4ω-6; ARA; Figure 22.1) and α-linolenic acid can be converted to eicosapentaenoic acid (20:5ω-3; EPA; Figure 22.1). Both arachidonic acid and EPA can be further metabolized, EPA ultimately giving rise to docosahexaenoic acid (22:6ω-3; DHA; Figure 22.1).
