Metabolism of cis-12-octadecenoic acid and trans-9,trans-12-octadecadienoic acid and their influence on lipogenic enzyme activities in mouse liver

High carbohydrate (65% glucose) diets containing cis-12-octadecenoic acid (12c-18:1) or trans-9,trans-12-octadecadienoic acid (9t,12t-18:2) were fed to weanling mice to investigate the influence of fatty acid structure on six hepatic enzyme activities involved in lipid metabolism. Results with these diets were compared to those with diets containing no fatty acids, saturated fatty acids; cis-9-octadecenoic acid (9c-18:1) and cis-9,cis-12-octadecadienoic acid (9c,12c-18:2). These comparisons show saturated fatty acids, 9c-18:1, 12c-18:1, and 9t,12t-18:2, had little or no influence on the activity levels of fatty acid synthetase, malic enzyme (EC 1.1.1.40)citrate cleavage enzyme (EC 4.1.3.8), glucose-6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 1.1.1.44) and acetyl-CoA carboxylase (EC 6.4.1.2). Neither 12c-18:1 nor 9t,12t-18:2 produced the dramatic enzyme-lowering effect exhibited by the diet containing 9c,12c-18:2 when compared to the diet devoid of fat. Thus, both the 9 and 12 bonds must be present in the same molecule. Also, at least one and probably both bonds must be in the cis configuration to depress liver enzyme activities. Capillary gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were both used for analysis of the methyl esters derived from the hepatic lipids. The GC and GC-MS data provided (a) direct evidence for incorporation of both isomers into hepatic lipids and (b) indirect evidence that 9t,12t-18:2 lowered liver delta 9-desaturase activity. In addition, since these products were found in the complex liver lipids, there is no doubt that the various enzymes concerned with activation and acylation utilize both of these isomeric fatty acids as substrates.