STIMULATION OF FATTY-ACID OXIDATION BY A 3-THIA FATTY-ACID REDUCES TRIACYLGLYCEROL SECRETION IN CULTURED RAT HEPATOCYTES

The present work shows that when mitochondrial beta-oxidation is stimu lated by the hypolipemic, non-beta-oxidizable fatty acid analogue tetr adecylthioacetic acid, there is a decrease in the secretion of triacyl glycerol in cultured rat hepatocytes. In order to study the effects of tetradecylthioacetic acid in cells with different fatty acid oxidatio n rates, cells were grown without or with L-carnitine supplement or wi th addition of the beta-oxidation inhibitor L-aminocarnitine. In cells grown without and with L-carnitine in the medium, the oxidation of [1 -C-14]oleic acid was stimulated by tetradecylthioacetic acid, whereas it was not significantly changed by palmitic acid. In cells grown with L-aminocarnitine, oxidation of [1-C-14]oleic acid was almost abolishe d both in the absence and in presence of tetradecylthioacetic acid. Th e effect of tetradecylthioacetic acid and palmitic acid on incorporati on of [1-C-14]oleic acid into triacylglycerol was similar under all co nditions. In the presence of L-carnitine, secretion of oleic acid-labe led triacylglycerol was reduced significantly more by tetradecylthioac etic acid than by palmitic acid. The effects of tetradecylthioacetic a cid and palmitic acid on secretion of oleic acid-labeled triacylglycer ol were reversed in cells grown with L-aminocarnitine, where palmitic acid was the stronger inhibitor. These results were substantiated by d etermination of mass of triacylglycerol secreted. jlr It is concluded that tetradecylthioacetic acid reduces secretion of triacylglycerol fr om rat hepatocytes mainly by acutely stimulating fatty acid oxidation.