LONG-TERM EFFECT OF TETRADECYLTHIOACETIC ACID - A STUDY ON PLASMA-LIPID PROFILE AND FATTY-ACID COMPOSITION AND OXIDATION IN DIFFERENT RAT ORGANS

Administration of tetradecylthioacetic acid (a 3-thia fatty acid) incr eases mitochondrial and peroxisomal P-oxidative capacity and carnitine palmitoyltransferase activity, but reduces free fatty acid and triacy lglycerol levels in plasma compared to palmitic acid-treated rats and controls. The decrease in plasma triacylglycerol was accompanied by a reduction (56%) in VLDL-triacylglycerol. Prolonged supplementation of tetradecylthioacetic acid caused a significant increase in lipogenic e nzyme activities (ATP-citrate lyase and acetyl-CoA carboxylase) and di acylglycerol acyltransferase, but did not affect phosphatidate phospho hydrolase. Plasma cholesterol, LDL- and HDL-cholesterol levels were re duced. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity was, h owever, stimulated in 3-thia fatty acid-treated rats compared to contr ols. In addition, the mRNAs of 3-hydroxy-3-methylglutaryl-coenzyme A r eductase and LDL-receptor were increased. Tetradecylthioacetic acid ad ministration affected the fatty acid composition in plasma and liver b y increasing the amount of monoenes, especially 18:1(n - 9), mostly at the expense of omega - 3 fatty acids. Compared to liver a large amoun t of tetradecylthioacetic acid accumulated in the heart, and this accu mulation was accompanied by an increase in omega - 3 fatty acids, part icularly 22:6(n - 3) and a decrease in omega - 6 fatty acids, mainly 2 0:4(n - 6). The results show that the hypolipidemic effect of tetradec ylthioacetic acid is sustained after prolonged administration and may, at least in part, be due to increased fatty acid oxidation and upregu lated LDL-receptor gene expression. The increase in lipogenic enzyme a ctivities as well as increased 3-hydroxy-3-methylglutaryl-coenzyme A r eductase activity, may be compensatory mechanisms to maintain cellular integrity, Decreased level of 20,4(n - 6) combined with increased ome ga - 3/omega - 6 ratio in cardiac tissue after tetradecylthioacetic ac id treatment may have influence on membrane dynamics and function.