Eicosanoids dietary linoleic acid effects

Figure 13.13. Effect of dietary linoleic acid on synthesis of active eicosanoids and metabolism. Pathophysiological actions result from faster eicosanoid formation by increased hydroperoxide levels. From Lands etal. (1986).

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... 

The perturbation of the incorporation of linoleic add metabolites into mammary gland lipids by CLA metabolism may lead to the hypothesis that CLA is able to create a mild arachidonic acid deficiency condition, in particular in the mammary tissue which is composed mainly of neutral lipids. In fact, because CLA and some of its metabolites are preferentially incorporated into neutral lipids (15), unlike linoleic acid, which is instead incorporated mainly into phospholipids, the preponderance of neutral lipids in the mammary tissue renders the competition between these two fatty acids more favorable toward CLA. It has been demonstrated that mammary tumorigenesis requires essential fatty acids, and eicosanoid inhibitors are able to reduce tumor incidence in experimental models (22). CLA, likely by decreasing the supply of arachidonic acid and inhibiting eicosanoid formation through its metabolites, may counteract arachidonic acid-derived eicosanoid action. Because the decrease of arachidonic acid, CLA metabolite incorporation, TEB density, and tumor incidence correlated with the (XA dietary intake, we can speculate that TEB density could also be modulated by eicosanoids. More data are required, however, to substantiate this hypothesis and to identify which eicosanoid(s) may be responsible for such effects. 

Arachidonic (all ds 5,8,11,14-eicosatetraenoic) acid has been shown to have equivalent or even greater activity than linoleic add, and linolenic (all d59,12,15-octadecadienoic) acid is about 1.5 times as effective as linoleic acid. Mammals cannot synthesise fatty acids with double bonds closer than carbon atom 9 from the terminal methyl group. Such acids have to be supplied in the diet. Linoleic add (18 2n-6) and a-linolenic acid (18 3 n-3) are thus dietary essentials. Arachidonic acid is synthesised in the body from linoleic acid. However, one of the steps in the synthesis, a A-6 desaturation, is rate-limiting and production may be slow and an exogenous supply advantageous (see Box 3.1). Linoleic and a-linolenic acids are referred to as the essential fatty acids (ERA). Like other polyunsaturated acids, they form part of various membranes and play a part in hpid transport and certain lipoprotein enzymes. In addition, they are the source materials for the synthesis of the eicosanoids. These include the prostaglandins, thromboxanes and leukotrienes, hormone-like substances that regulate... 

Although most hpids required for cell structure, fuel storage, or hormone synthesis can be synthesized from carbohydrates or proteins, we need a minimal level of certain dietary hpids for optimal health. These hpids, known as essential fatty acids, are required in our diet because we cannot synthesize fatty acids with these particular arrangements of double bonds. The essential fatty acids a-linoleic and a-linolenic acid are supphed by dietary plant oils, and eicosapentaenoic acid (ERA) and docosa-hexaenoic acid (DHA) are supplied in fish oils. They are the precursors of the eicosanoids (a set of hormone-like molecules that are secreted by cells in small quantities and have numerous important effects on neighboring cells). The eicosanoids include the prostaglandins, thromboxanes, leukotrienes, and other related compounds. 

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