Abstract
The present work shows that when mitochondrial beta-oxidation is stimulated by the hypolipemic, non-beta-oxidizable fatty acid analogue tetradecylthioacetic acid, there is a decrease in the secretion of triacylglycerol in cultured rat hepatocytes. In order to study the effects of tetradecylthioacetic acid in cells with different fatty acid oxidation rates, cells were grown without or with L-carnitine supplement or with addition of the beta-oxidation inhibitor L-aminocarnitine. In cells grown without and with L-carnitine in the medium, the oxidation of [1-14C]oleic acid was stimulated by tetradecylthioacetic acid, whereas it was not significantly changed by palmitic acid. In cells grown with L-aminocarnitine, oxidation of [1-14C]oleic acid was almost abolished both in the absence and in presence of tetradecylthioacetic acid. The effect of tetradecylthioacetic acid and palmitic acid on incorporation of [1-14C]oleic acid into triacylglycerol was similar under all conditions. In the presence of L-carnitine, secretion of oleic acid-labeled triacylglycerol was reduced significantly more by tetradecylthioacetic acid than by palmitic acid. The effects of tetradecylthioacetic acid and palmitic acid on secretion of oleic acid-labeled triacylglycerol were reversed in cells grown with L-aminocarnitine, where palmitic acid was the stronger inhibitor. These results were substantiated by determination of mass of triacylglycerol secreted. It is concluded that tetradecylthioacetic acid reduces secretion of triacylglycerol from rat hepatocytes mainly by acutely stimulating fatty acid oxidation.
Highlights
Oxidation is stimulated by the hypolipemic, non-0-oxidizable fatty acid analogue tetradecylthioaceticacid, there is a decrease in the secretion of triacylglycerol in cultured rat hepatocytes
tetradecylthioacetic acid (TTA) was incorporated into synthesized triacylglycerol at a rate about two-thirds that of the normal fatty acids, while its secretion in triacylglycerol into the incubation medium was about one-half of the normal fatty acids at 0.5 mM
In previous work we have shown that the hypolipemic compound tetradecylthioacetic acid (TTA) stimulates fatty acid oxidation in isolated rat hepatocytes [13]
Summary
Oleic acid and palmitic acid were oxidized 3 times faster when the fatty acid concentration was increased from 0.25 to 0.5 mM, while the oxidation of TTA did not increase. ; C, L-aminocarnitine (50 pM) and {l-'*C]oleic acid (0.2 mM, 0.5 mCiimmo1) without or with increasing concentrations of palmitic acid (0)or TTA (0).Ratio fatty acid/BSA was 2.5:l. TTA significantly stimulated oxidation of oleic acid in absence and presence of L-carnitine. Calculating oxidation as percentage of oleic acid oxidation alone (control value), the stimulatoryeffect of TTA in presence of L-carnitine differed from that of palmitic acid with a Pvalue cO. at all concentrations (Fig. 2B). Oxidation of oleic acid was not significantly changed in the presence of increasing concentrations of palmitic acid under all three culture conditions
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