Delta 8 desaturation in vivo of deuterated eicosatrienoic acid by mouse liver.

Abstract

In vitro evidence has been reported for an alternate pathway that involves delta 8 desaturation of n-6 and n-3 polyunsaturated fatty acids (PUFA). The present study was designed to allow detection of delta 8 desaturation in vivo and to provide an estimation of the relative contribution of delta 8 desaturation to the in vivo synthesis of n-3 fatty acids. Male adult ICR mice were fed a semisynthetic fat-free diet for eight days, and then the diets were supplemented for three days with deuterated 11,14,17-eicosatrienoic acid (20:3-d8) labeled at the 3,3,4,4,8,8,9,9 carbon positions. Analysis of liver total lipid by gas chromatography/mass spectroscopy indicates that the total deuterated fatty acids contained 22.3% 20:3n-3-d8 and 28.9% of metabolites formed by elongation and delta 5 desaturation of 20:3n-3-d8. Deuterated metabolites resulting from retroconversion to 18:3-d6 and subsequent metabolism by classical pathways represented 35.3% of the total deuterated fatty acids. The retroconversion product (18:4n-3-d6) of 20:4n-3-d6 and/or -d8 was 9.0% of the total. A minor percentage (4.4%) of the products identified (20:4n-3-d6, 20:5n-3-d6, 22:5n-3-d6, 22:6n-3-d5 and 24:6n-3-d5) were formed by delta 8 desaturation. This study provides the first clear evidence of delta 8 desaturation in vivo in the mouse liver. Whether delta 8 desaturation would have a greater importance in vivo when the delta 6 desaturase pathway is disrupted remains to be determined.