The biological function of long chain (n-3) and (n-6) fatty acids derived from dietary linoleate and linolenate is not known. Streptozotocin induced diabetes or dietary fat modification alters the levels of these and other unsaturated fatty acids in various tissue lipids in unique but different ways. Studies will be carried out to define what reactions in (n-3) and (n-6) unsaturated fatty acid biosynthesis are altered by diabetes and how subsequent insulin therapy or fructose feeding modifies liver microsomal fatty acyl-CoA chain elongation and desaturation reaction rates and also tissue lipid fatty acid composition. Enzymatic and in vivo experiments will be carried out to determine the pathway by which a double bond is inserted at position-4 in unsaturated fatty acid biosynthesis. Long chain (n-3) and (n-6) unsaturated fatty acids will be incubated with blood platelets, artery and kidney microsomes to define whether they serve as precursors for prostaglandins. The physiological response of these prostaglandins on the artery and platelet will be determined. The overall objective of these studies is to define what relationship exists between factors regulating tissue lipid unsaturated fatty acid composition, prostaglandin production and physiological function as mediated by the total pool of prostaglandins. These studies will focus on the long chain (n-3) and (n-6) fatty acids because their levels are altered in tissue lipids in the diabetic, the factors regulating their synthesis is not known and it has never been established whether they are converted to oxygenated derivatives by cyclooxygenase or lipoxygenase.
