Abstract
In the liver of rats, monocarboxylic 3-thia fatty acids, tridecylthioacetic acid (C13-S-acetic acid) and tetradecylthioacetic acid (C14-S-acetic acid), increase the mRNA levels of delta 9-desaturase both in a time- and dose-dependent manner. The increased delta 9-desaturase mRNA levels were accompanied by increased delta 9-desaturase activity and increased amounts of oleic acid (18:1 n-9) and delta 9-desaturated C14-S-acetic acid. delta 9-Desaturated C14-S-acetic acid was only detected in phospholipid and cholesterolester species after C14-S-acetic acid treatment. In contrast, C14-S-acetic acid was detected in all the different hepatic lipid fractions, but mainly in the phospholipids. Moreover, C13-S-acetic acid and C14-S-acetic acid were detected in both liver and very low density lipoprotein (VLDL). No delta 9-desaturated 3-thia fatty acid products, however, were found in VLDL. Administration of mono- and dicarboxylic 3-thia fatty acids to rats induced liver expression of the fatty acyl-CoA oxidase gene. After 1 week of C14-S-acetic acid treatment, the levels of fatty acyl-CoA oxidase mRNA increased 5-fold, whereas the delta 9-desaturase mRNA was increased about 1.8-fold. Both fatty acyl-CoA oxidase and delta 9-desaturase mRNA increased about 8-fold after 12 weeks of treatment with C14-S-acetic acid. In conclusion, this study demonstrates that C14-S-acetic 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 the VLDL. The peroxisome-proliferating monocarboxylic thia fatty acids are good substrates for desaturases, as delta 9-desaturated metabolites of monocarboxylated thia acids were formed in the liver. Modification of delta 9-desaturation, however, appears not to be related to peroxisome proliferation.
Highlights
In the liver of rats, monocarboxylic 3-thia fatty acids, tridecylthioacetic acid (CI3-Saceticacid) and tetradecylthioacetic acid (C,-Sacetic acid), increase the mRNA levels of Agdesaturase both in a time- and dose-dependent manner
Given that the fatty acid composition of glycerolipids has an important role in controlling the lipoprotein metabolism, we report that C14-Sacetic acid upregulates A'desaturase mRNA levels and activity in rat liver concomitant with the formation of a A'desaturated metabolite of ClrSacetic acid, Le., the saturated 3-thia fatty acid can be converted to a monoenic 3-thia fatty acid in vivo
We demonstrated that the fatty acid composition in total liver homogenates changes after long-term administration of tetradecylthioacetic acid (C14-Saceticacid) [20]
Summary
In the liver of rats, monocarboxylic 3-thia fatty acids, tridecylthioacetic acid (CI3-Saceticacid) and tetradecylthioacetic acid (C,,-Sacetic acid), increase the mRNA levels of Agdesaturase both in a time- and dose-dependent manner. The enzymatic activity of peroxisomal fatty acyl-CoA oxidase was measured in the post-nuclear fraction of rat livers by the coupled assay described by Small, Burdett, and Connock [8]. The fractions containing triacylglycerol, cholesteryl esters, and phospholipids as well as the plasma lipid extracts underwent hydrolysis in 15% methanolic KOH for 45 min at 65"C, followed by acidification with HC1 and extraction of the liberated fatty acids with hexane.
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