N-6 PUFAs

Dietary polyunsaturated fatty acids (PUFAs), especially the n-3 series that are found in marine fish oils, modulate a variety of normal and disease processes, and consequently affect human health. PUFAs are classified based on the position of double bonds in their lipid structure and include the n-3 and n-6 series. Dietary n-3 PUFAs include a-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) whereas the most common n-6 PUFAs are linoleic acid, y-linolenic acid, and arachidonic acid (AA). AA is the primary precursor of eicosanoids, which includes the prostaglandins, leukotrienes, and thromboxanes. Collectively, these AA-derived mediators can exert profound effects on immune and inflammatory processes. Mammals can neither synthesize n-3 and n-6 PUFAs nor convert one variety to the other as they do not possess the appropriate enzymes. PUFAs are required for membrane formation and function... 

Platelets aggregation stimulation. Fruit juice, administered intravenously by infusion to dogs at a dose of 5 mL/min, was active. Total infusion was 300 mL h Oil, administered orally to six New Zealand white rabbits fed a commercial diet supplemented with 60 g/kg of coconut oil low in all PUFA for 60 days, produced a platelets aggregation induced by both thrombin and collagen significantly lower with either fish or linseed oil (n-3 PUFA), than with corn oil (n-6 PUFA) or the low PUFA coconut oil . 

Therefore, when COX-associated biochemical reactions are intensively associated with EPA due to increased EPA levels and decreased proinflammatory AA levels, less harmful and significantly reduced inflammatory status can be expected. Thus, increased n-3 PUFA levels compared to n-6 PUFA can impart significant beneficial health effects against inflammation. Also, it has been recently suggested that increased n-3 PUFA levels in patients can improve the outcome of critically ill patients (Ott et al., 2011). 

The n-6 PUFAs have been shown to upregulate COX-2 expression,80 whereas n-3 PUFAs have been shown to suppress its expression in tumors,81,82 in association with decreased proliferation of cancer cells and reduced tumor angiogenesis.83 n-3 PUFAs have also been shown to suppress tumor growth via a COX-independent pathway.84 DHA, in comparison with LA, has also been shown to decrease the expression of other oncogenes implicated in tumor promotion including ras85 and bcl-2 expression,86 resulting in inhibition of mitosis and enhanced apoptosis of cancer cells, respectively. 

The modulatory effect of n-3 PUFAs on eicosanoid production could also be achieved at the enzyme level. The action of n-3 fatty acids that decreases the production of PGE2 could be an effect of down-regulation of COX-2 activity in local tissues (129, 130). In a study with rats, dietary n-6 PUFA up-regulated COX-2 and, to some extent, COX-1 expression leading to a concomitant increase in COX enzyme activity and prostaglandin synthesis, but fats containing added menhaden oil (high in n-3 PUFAs) had an opposite effect (131). 

Apart from the above mentioned enzymes, there also exist a few enzymes involved in PUFA metabolic pathways that have recently been found. One of them is a novel n-3 fatty acid desaturase, isolated from an EPA-rich fungus, Saprolegnia diclina [248]. The gene was isolated by PCR amplification from a fungus cDNA library and then, expressed in S. cerevisiae, which was cultured in the presence of several FA as substrates. The study showed that the recombinant protein could exclusively desaturase C20 n-6 PUFAs, with preference for AA which was converted into EPA. This represents a completely novel and different activity from any organism previously described, and its potential for use in EPA production in transgenic oilseed crops has been outlined. 

The metabolism of n-3 and n-6 PUFAs is interlinked, as they compete for enzymes and metabolic substrates at all levels. Therefore, relative as well as absolute dietary intake is relevant in the determination of tissue n-3 and n-6 fatty acid levels. The Western diet typically contains high levels of n-6 fatty acids, as these are components of most animal and vegetable fats. Dietary sources of n-3 PUFA are varied. The most plentiful sources are fish, shellfish, and marine products, which contain large amounts of EPA and DHA. Certain plant oils, such as rapeseed (canola), soybean, and perilla contain large amounts of LNA (Crawford Sinclair, 1972 Sinclair, 1975). Although beef and lamb do contain n-3 PUFAs, both the absolute content and the n-3 n-6 ratio of PUFAs within these meats is low. 

Burr and Burr (1929) highlighted the importance of certain fats in the human diet and demonstrated that dietary deprivation of the essential fatty acids was deleterious to health. They concluded that the n-6 PUFAs were most important to function in mammals because their omission resulted in overt systemic dysfunction. Conversely, it has been shown that deprivation of n-3 PUFAs results in subtle dysfunction across a range of behavioral and physiological modalities. 

Fig. 4, Effect of fat content of diet on body weight of lean and obese mice. Lean (In/ln) and obese (ob/ob) mice were fed a n-6-PUFA-rich (evening primi ose oil, closed bars) or n-3 PUFA-rich (cod-liver oil, hatched bars)-based diet for 16 wk and the effect on final body weight determined. (Adapted from Cunnane et al., 1986)...

Very low levels of n - 3 and n - 6 PUFA are present in the Harderian gland, indicating that the lipids of this gland are mainly composed of SFA and MUFA of the n - 9 series. 

The rationale for n-3 and n-6 polyunsaturated long-chain fatty acid (PUFA) supplementation in the treatment of AD resides in the antiinflammatory effects of these lipid compounds. Over the past few years, a growing body of evidence has demonstrated that n-3 and n-6 PUFAs alleviate a number of inflammatory diseases. Actually, the first evidence of the importance of dietary intake of these lipids was derived from epidemiological observations about the very low incidence of chronic inflammatory condition in Eskimos. 

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