Effects of Non-beta-oxidizable Sulfur-substituted Fatty Acid Analogues on Synthesis and Secretion of Triacylglycerol and Cholesterol in Cultured Rat Hepatocytes

Overview

Journal Lipids

Specialty Biochemistry

Date 1995 Nov 1

PMID 8569438

Authors

J Skorve

A C Rustan

R K Berge

Affiliations

Soon will be listed here.

Abstract

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.

References

Nossen J, Rustan A, Gloppestad S, Malbakken S, Drevon C . Eicosapentaenoic acid inhibits synthesis and secretion of triacylglycerols by cultured rat hepatocytes. Biochim Biophys Acta. 1986; 879(1):56-65. DOI: 10.1016/0005-2760(86)90266-3. View

Dixon J, Ginsberg H . Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells. J Lipid Res. 1993; 34(2):167-79. View

Aarsland A, Berge R, Bremer J, Aarsaether N . The hypolipidemic peroxisome-proliferating drug, bis(carboxymethylthio)-1.10 decane, a dicarboxylic metabolite of tiadenol, is activated to an acylcoenzyme A thioester. Biochim Biophys Acta. 1990; 1033(2):176-83. DOI: 10.1016/0304-4165(90)90009-l. View

MARSH J, Topping D, Nestel P . Comparative effects of dietary fish oil and carbohydrate on plasma lipids and hepatic activities of phosphatidate phosphohydrolase, diacylglycerol acyltransferase and neutral lipase activities in the rat. Biochim Biophys Acta. 1987; 922(2):239-43. DOI: 10.1016/0005-2760(87)90160-3. View

Spydevold O, Bremer J . Induction of peroxisomal beta-oxidation in 7800 C1 Morris hepatoma cells in steady state by fatty acids and fatty acid analogues. Biochim Biophys Acta. 1989; 1003(1):72-9. DOI: 10.1016/0005-2760(89)90101-x. View

McGarry J, Foster D . Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem. 1980; 49:395-420. DOI: 10.1146/annurev.bi.49.070180.002143. View

Yamamoto M, Fukuda N, Triscari J, Sullivan A, Ontko J . Decreased hepatic production of very low density lipoproteins following activation of fatty acid oxidation by Ro 22-0654. J Lipid Res. 1985; 26(10):1196-204. View

McGarry J, Mannaerts G, Foster D . A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest. 1977; 60(1):265-70. PMC: 372365. DOI: 10.1172/JCI108764. View

Duerden J, Marsh B, Burnham F, Gibbons G . Regulation of hepatic synthesis and secretion of cholesterol and glycerolipids in animals maintained in different nutritional states. Biochem J. 1990; 271(3):761-6. PMC: 1149628. DOI: 10.1042/bj2710761. View

10.

Rustan A, Nossen J, CHRISTIANSEN E, Drevon C . Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A:1,2-diacylglycerol acyltransferase. J Lipid Res. 1988; 29(11):1417-26. View

11.

Asiedu D, Demoz A, Skorve J, GRAV H, Berge R . Acute modulation of rat hepatic lipid metabolism by sulphur-substituted fatty acid analogues. Biochem Pharmacol. 1995; 49(7):1013-22. DOI: 10.1016/0006-2952(94)00460-4. View

12.

Skrede S, Bremer J, Berge R, Rustan A . Stimulation of fatty acid oxidation by a 3-thia fatty acid reduces triacylglycerol secretion in cultured rat hepatocytes. J Lipid Res. 1994; 35(8):1395-404. View

13.

Hvattum E, GRAV H, Bremer J . Hormonal and substrate regulation of 3-thia fatty acid metabolism in Morris 7800 C1 hepatoma cells. Biochem J. 1993; 294 ( Pt 3):917-21. PMC: 1134549. DOI: 10.1042/bj2940917. View

14.

Berge R, Aarsland A, Kryvi H, Bremer J, Aarsaether N . Alkylthio acetic acids (3-thia fatty acids)--a new group of non-beta-oxidizable peroxisome-inducing fatty acid analogues--II. Dose-response studies on hepatic peroxisomal- and mitochondrial changes and long-chain fatty acid metabolizing enzymes in.... Biochem Pharmacol. 1989; 38(22):3969-79. DOI: 10.1016/0006-2952(89)90676-x. View

15.

Asiedu D, Skorve J, Willumsen N, Demoz A, Berge R . Early effects on mitochondrial and peroxisomal beta-oxidation by the hypolipidemic 3-thia-fatty acids in rat livers. Biochim Biophys Acta. 1993; 1166(1):73-6. DOI: 10.1016/0005-2760(93)90285-h. View

16.

Skrede S, Bremer J . Acylcarnitine formation and fatty acid oxidation in hepatocytes from rats treated with tetradecylthioacetic acid (a 3-thia fatty acid). Biochim Biophys Acta. 1993; 1167(2):189-96. DOI: 10.1016/0005-2760(93)90161-2. View

17.

Gibbons G, Burnham F . Effect of nutritional state on the utilization of fatty acids for hepatitic triacylglycerol synthesis and secretion as very-low-density lipoprotein. Biochem J. 1991; 275 ( Pt 1):87-92. PMC: 1150017. DOI: 10.1042/bj2750087. View

18.

Fukuda N, Ontko J . Interactions between fatty acid synthesis, oxidation, and esterification in the production of triglyceride-rich lipoproteins by the liver. J Lipid Res. 1984; 25(8):831-42. View

19.

Folch J, Lees M, SLOANE STANLEY G . A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957; 226(1):497-509. View

20.

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View