UP-REGULATED DELTA(9)-DESATURASE GENE-EXPRESSION BY HYPOLIPIDEMIC PEROXISOME-PROLIFERATING FATTY-ACIDS RESULTS IN INCREASED OLEIC-ACID CONTENT IN LIVER AND VLDL - ACCUMULATION OF A DELTA(9)-DESATURATED METABOLITE OF TETRADECYLTHIOACETIC ACID

In the liver of rats, monocarboxylic 3-thia fatty acids, tridecylthioa cetic acid (C-13-S-acetic acid) and tetradecylthioacetic acid (C-14-S- acetic acid), increase the mRNA levels of Delta(9)-desaturase both in a time- and dose-dependent manner. The increased Delta(9)-desaturase m RNA levels were accompanied by increased Delta(9)-desaturase activity and increased amounts of oleic acid (18:1 n-9) and Delta(9)-desaturate d C-14-S-acetic acid. Delta(9)-Desaturated C-14-S-acetic acid was only detected in phospholipid and cholesterolester species after C-14-S-ac etic acid treatment. In contrast, C-14-S-acetic acid was detected in a ll the different hepatic lipid fractions, but mainly in the phospholip ids. Moreover, C-14-S-acetic acid and C-14-S-acetic acid were detected in both liver and very Io iv density lipoprotein (VLDL). No Delta(9)- desaturated 3-thia fatty acid products, however, were found in VLDL. A dministration of mono- and dicarboxylic 3-thia fatty acids to rats ind uced liver expression of the fatty acyl-CoA oxidase gene. After 1 week of C-14-S-acetic acid treatment, the levels of fatty acyl-CoA oxidase mRNA increased 5-fold, whereas the Delta(9)-desaturase mRNA was incre ased about 1.8-fold. Both fatty acyl-CoA oxidase and Delta(9)-desatura se mRNA increased about 8-fold after 12 weeks of treatment with C-14-S -acetic acid. In conclusion, this study demonstrates that C-14-S-aceti c acid increases rat Delta(9)-desaturase gene expression and activity and that changes in hepatic lipids, e.g., 18:1 n-9, are reflected in t he VLDL. The peroxisome-proliferating monocarboxylic thia fatty acids are good substrates for desaturases, as Delta(9)-desaturated metabolit es of monocarboxylated thia acids were formed in the liver. Modificati on of Delta(9)-desaturation, however, appears not to be related to per oxisome proliferation.