δ8 desaturationin vivo of deuterated eicosatrienoic acid by mouse liver

In vitro evidence has been reported for an alternate pathway that involves δ8 desaturation of n-6 and n-3 polyunsaturated fatty acids (PUFA). The present study was designed to allow detection of δ8 desaturationin vivo and to provide an estimation of the relative contribution of δ8 desaturation to thein 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 δ5 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 δ8 desaturation. This study provides the first clear evidence of δ8 desaturationin vivo in the mouse liver. Whether δ8 desaturation would have a greater importancein vivo when the δ6 desaturase pathway is disrupted remains to be determined.