Early modulation of genes encoding peroxisomal and mitochondrial beta-oxidation enzymes by 3-thia fatty acids

The aim of the present study was to elucidate the effects of a single dose of 3-thia fatty acids (tetradecylthioacetic acid and 3-thiadicarboxylic aci d) over a 24-hr study period on the expression of genes related to peroxiso mal and mitochondrial beta-oxidation in liver of rats. The plasma triglycer ide level decreased at 2-4 hr, 4-8 hr, and 8-24 hr, respectively, after a s ingle dose of 150, 300, or 500 mg of 3-thia fatty acids/kg body weight. Fou r to eight hours after administration of 3-thia fatty acids, a several-fold -induced gene expression of peroxisomal multifunctional protein, fatty acyl -CoA oxidase (EC 1.3.3.6), fatty acid binding protein, and 2,4-dienoyl-CoA reductase (EC 1.3.1.43) resulted, concomitant with increased activity of 2, 4-dienoyl-CoA reductase and fatty acyr-CoA oxidase. The expression of carni tine palmitoyltransferase-I and carnitine palmitoyltransferase-II increased at 2 and 4 hr, respectively, although at a smaller scale. In cultured hepa tocytes, 3-thia fatty acids stimulated fatty acid oxidation after 4 hr, and this was both L-carnitine- and L-aminocamitine-sensitive. The hepatic cont ent of eicosapentaenoic acid and dacosahexaenoic acid decreased throughout the study period. In contrast, the hepatic content of oleic acid tended to increase after 24 hr and was significantly increased after repeated adminis tration of 3-thia fatty acids. Similarly, the expression of Delta(9)-desatu rase was unchanged during the 24-hr-study, but increased after feeding for 5 days. To conclude, carnitine palmitoyltransferase-I expression seemed to be induced earlier than 2,4-dienoyl-CoA reductase and fatty acid binding pr otein, and not later than the peroxisomal fatty acyl-CoA oxidase. The expre ssion of Delta(9)-desaturase showed a more delayed response. BIOCHEM PHARMA COL 56;12:1571-1582, 1998. (C) 1998 Elsevier Science Inc.