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. 2012;2012:539426.
doi: 10.1155/2012/539426. Epub 2012 Apr 5.

Health implications of high dietary omega-6 polyunsaturated Fatty acids

E Patterson  1 , R Wall, G F Fitzgerald, R P Ross, C Stanton
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Health implications of high dietary omega-6 polyunsaturated Fatty acids

E Patterson et al. J Nutr Metab. .
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Abstract

Omega-6 (n-6) polyunsaturated fatty acids (PUFA) (e.g., arachidonic acid (AA)) and omega-3 (n-3) PUFA (e.g., eicosapentaenoic acid (EPA)) are precursors to potent lipid mediator signalling molecules, termed "eicosanoids," which have important roles in the regulation of inflammation. In general, eicosanoids derived from n-6 PUFA are proinflammatory while eicosanoids derived from n-3 PUFA are anti-inflammatory. Dietary changes over the past few decades in the intake of n-6 and n-3 PUFA show striking increases in the (n-6) to (n-3) ratio (~15 : 1), which are associated with greater metabolism of the n-6 PUFA compared with n-3 PUFA. Coinciding with this increase in the ratio of (n-6) : (n-3) PUFA are increases in chronic inflammatory diseases such as nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, obesity, inflammatory bowel disease (IBD), rheumatoid arthritis, and Alzheimer's disease (AD). By increasing the ratio of (n-3) : (n-6) PUFA in the Western diet, reductions may be achieved in the incidence of these chronic inflammatory diseases.

Figures

Figure 1
Metabolism of n-6 and n-3 PUFA. The metabolism of PUFA is a complex process involving several enzymes of desaturation, elongation, and β-oxidation. Shown here is the pathway of both n-6 and n-3 PUFA metabolism to more unsaturated, long-chain members of each family. Also shown are their respective eicosanoid derivatives. Data elaborated from [21].
Figure 2
Effects of unbalanced n-6 : n-3 dietary fatty acid intake on development of various diseases of inflammation. Dietary imbalance in the consumption of n-6 and n-3 PUFA, representative of the Western diet. Greater consumption of n-6 PUFA leads to an increase in their metabolism to their LC-PUFA derivatives (AA). Decreases in n-3 PUFA consumption leads to a decrease in their metabolism to their LC-PUFA derivatives (EPA/DHA). The increase in AA in cell membrane phospholipids leads to an increase in COX and LOX enzyme production of AA-derived eicosanoids and a decrease in EPA/DHA-derived eicosanoids, leading to an increase in inflammation and proinflammatory cytokine production. This in turn leads to a decrease in PPARα gene expression, while there is an increase in both SREBP-1c and NFκB gene expression. This change in gene expression can also cause an increase in lipogenesis, as well as increasing inflammation. The result is an increase in various diseases of inflammation, some of which are highlighted in the figure.
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