METABOLITES OF CIS,TRANS, AND TRANS,CIS ISOMERS OF LINOLEIC-ACID IN MICE AND INCORPORATION INTO TISSUE-LIPIDS

Metabolism of octadecadienoic acid isomers in weanling mice was studied by feeding fat-free diets supplemented with 2% by weight of cis-9,trans-12-octadecadienoic acid (c,t-18:2-d0), tetradeuterated trans-9,cis-12-octadecadienoic acid (t,c-18:2-d4) or dideuterated cis-9,cis-12-octadecadienoic acid (c,c-18:2-d2). Rates for conversion of c,t-18:2-d0 and c,c-18:2-d2 to c,t-20:4-d0 and c,c-20:4-d2 were identical and both were 5-times higher than conversion of t,c-18:2-d4 to t,c-20:4-d4. Accumulation of t,c-18:2-d4 in liver lipids was 2-4-times higher than for c,t-18:2-d0 or c,c-18:2-d2. The t,c-18:2 diet significantly increased with the 20:3(n - 9) and total lipid concentrations in liver but not in heart, plasma or brain. The 20:3(n - 9)/20:4(n - 6) ratio in the liver lipids was 2-4-times higher for t,c-18:2-d4 than c,c-18:2-d2 fed mice. The position of the trans bond had a marked influence on the distribution of the various intermediate desaturation and elongation products. Intermediate metabolite data for the liver lipids indicated t,c-18:2-d4 was preferentially converted to 5c,11c,14t-20:3 ('dead end' product) rather than to t,c-20:4. Concentration of the 18:3(n - 6) metabolite of c,t-18:2-d0 was about 10-times greater than the 18:3(n - 6) metabolite of c,c-18:2-d2. Conversely, the concentration of the normal 20:3(n - 6) metabolite from c,c-18:2-d2 was 4-times higher than the 20:3(n - 6) metabolite of c,t-18:2-d0. Compared to the c,c-18:2 diet, the t,c- and c,t-18:2 diets significantly increased the total n - 3, but not the total n - 6 fatty acid content of heart lipids. These results illustrate that the position of the trans double-bond influences a variety of enzyme activities and the isomers differ in their physiological effects.