EFFECTS OF DIETARY LINOLENATE ON ARACHIDONATE

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The objective of the proposed study is to evaluate the efficacy of dietary linolenic acid (18:3n-3), as compared to eicosapentaenoic acid (20:5n-3) or docosahexaenoic acid (22:6n-3) which are abundant in fish oil, to inhibit the formation of eicosanoids derives from arachidonic acid (20:4n-6) in rat tissues. The suggested beneficial effects of 20:5n-3 in reducing thrombogenic potential are considered to be primarily due to its competitive inhibition of the conversion of 20:4n-6 to thromboxane A2 (TXA2), and reduction of the 20:4n-6 level in platelets by displacement. An important question can be raised as to whether another type of dietary n-3 fatty acid can achieve similar or even more beneficial effects than 20:5n-3. This applicant proposes that dietary 18:3n-3 inhibits the conversion of linoleic acid (18:3n-6) to 20:4n-6. It also inhibits the formation of cyclooxygenase-derived products of 20:4n-6. Furthermore, 18:3n-3 is not a substrate for leukotrienes (LT), whereas 20:5n-3 is a preferred substrate for 5-lipoxygenase leading to the formation of pentaene LTs. Thus, dietary 18:3n-3 may be a more effective inhibitor than 20:5n- 3 for the biosynthesis of LTs. The specific aim is to compare 18:3n-3 with 20:5n-3 or 22:6n-3 for its effects on: (1) levels of eicosanoid precursor acids in free fatty acid fractions and tissue phospholipids, and (2) the formation of eicosanoids derived both from 20:4n-6 and 20:5n-3 in tissues. Rats will be fed graded amounts of purified 18:3n-3, 20:5n-3 or 22:6n-3 in the presence of a constant amount of 18:2n-6 for 12 weeks. Eicosanoids synthesized in tissues will be determined by radioimmunoassay and immunochromatographic assay. The long term objective is to establish the desirable ratio of n-3 to n-6 fatty acids in our diets to reduce certain risks of coronary heart disease. Presently, most dietary guidelines use polyunsaturated fatty acids (PUFA) without differentiating types of PUFA (n-3 or n-6). In the future, this ratio may need to be specified in the dietary guidelines.