Effects of non-beta-oxidizable sulfur-substituted fatty acid analogues on synthesis and secretion of triacylglycerol and cholesterol in cultured rat hepatocytes.
The mechanisms behind the hypolipidemic effect of two sulfur-substituted fatty acid analogues, 3-thiadicarboxylic acid and tetradecylthioacetic acid, have been investigated in cultured hepatocytes. There was a dose-dependent reduction in incorporation of [3H] water into triacylglycerol and diacylglycerol when tetradecylthioacetic acid was added to rat hepatocytes cultured in the presence of 200 muM oleic acid. Tetradecylthioacetic acid also increased the oxidation of [14C]palmitic acid compared to oleic acid, inhibited the incorporation of radiolabeled precursors into diacylglycerol to a greater extent than into triacylglycerol, and reduced the secretion of triacylglycerol more than its synthesis. A stimulation, rather than a reduction, in glycerolipid synthesis and secretion by oxidation of fatty acids and reduces the synthesis and secretion of glycerolipids. 3-Thiadicarboxylic acid reduces the synthesis and secretion of both glycerolipids and cholesterol to approximately the same extent without a concomitant increase in the oxidation of fatty acids.
Skorve
J
J
Department of Clinical Biology, University of Bergen, Haukeland University Hospital, Norway.
Rustan
A C
AC
Berge
R K
RK
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D051381:Rats; D013440:Sulfides / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism*; D014316:Tritium; D014867:Water / Q000378:metabolism
D003998:Dicarboxylic Acids; D009829:Oleic Acids; D010169:Palmitic Acids; D013440:Sulfides; D014280:Triglycerides; D014867:Water; D014316:Tritium; D019301:Oleic Acid; D019308:Palmitic Acid; C062079:1,10-bis(carboxymethylthiodecane); C062078:1-(carboxymethylthio)tetradecane; D002784:Cholesterol; D005990:Glycerol