Effect of 3-thia fatty acids on the lipid composition of rat liver, lipoproteins, and heart.

To investigate the importance of factors influencing the fatty acid composition, lipid and lipoprotein metabolism in the rat, the effect of 3-thia fatty acids of chain-length ranging from octyl- to hexadecylthioacetic acid were studied. In liver, very low density lipoprotein (VLDL), and low density lipoprotein (LDL), the hypolipidemic 3-thia fatty acids, namely C12-S-acetic acid to C14-S-acetic acid increased the amount of monoenes, especially oleic acid (18:ln-9). In contrast, the content of polyunsaturated fatty acids in liver, VLDL, and LDL decreased, mostly attributed to a reduction of eicosapentaenoic acid (EPA, 20:5n-3). Noteworthy, the hypolipidemic 3-thia fatty acids reduced the amount of arachidonic acid (AA, 20:4n-6) in LDL and HDL. 3-Thia fatty acids accumulated in the liver. In heart, as in liver, 3-thia fatty acids replaced fatty acids of chain-length homologues. In contrast to liver, we were unable to detect any changes in 18:ln-9. However, the n-3 polyunsaturated fatty acid content increased, particularly 20:5n-3 and docosahexaenoic acid (DHA, 22:6n-3) leading to an increased n-3/n-6 ratio. In conclusion, this study demonstrates that hypolipidemic 3-thia fatty acids change the fatty acid composition of organs and lipoproteins. These changes are linked to the expression and activity of hepatic delta9-desaturase, fatty acid oxidation, and displacement of normal fatty acids by 3-thia fatty acids. The fatty acid composition is regulated differently in liver and heart after administration of hypolipidemic 3-thia fatty acids.

[1]  L. Madsen,et al.  Up-regulated delta 9-desaturase gene expression by hypolipidemic peroxisome-proliferating fatty acids results in increased oleic acid content in liver and VLDL: accumulation of a delta 9-desaturated metabolite of tetradecylthioacetic acid. , 1997, Journal of lipid research.

[2]  L. Frøyland,et al.  Long-term effect of tetradecylthioacetic acid: a study on plasma lipid profile and fatty acid composition and oxidation in different rat organs. , 1996, Biochimica et biophysica acta.

[3]  L. Frøyland,et al.  A hypolipidemic peroxisome proliferating fatty acid induces polydispersity of rat liver mitochondria. , 1996, Biology of the cell.

[4]  L. Frøyland,et al.  Tetradecylthioacetic acid incorporated into very low density lipoprotein: changes in the fatty acid composition and reduced plasma lipids in cholesterol-fed hamsters. , 1995, Journal of lipid research.

[5]  R. Berge,et al.  Hepatic fatty acid metabolism as a determinant of plasma and liver triacylglycerol levels. Studies on tetradecylthioacetic and tetradecylthiopropionic acids. , 1995, European journal of biochemistry.

[6]  R. Berge,et al.  Gas chromatographic measurement of 3- and 4-thia fatty acids incorporated into various classes of rat liver lipids during feeding experiments. , 1994, Journal of chromatography. B, Biomedical applications.

[7]  R. Berge,et al.  Impact of cytochrome P450 system on lipoprotein metabolism. Effect of abnormal fatty acids (3-thia fatty acids). , 1994, Pharmacology & therapeutics.

[8]  M. Rudling,et al.  Effect of 3-thiadicarboxylic acid on lipid metabolism in experimental nephrosis. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[9]  J. Bremer,et al.  Hormonal and substrate regulation of 3-thia fatty acid metabolism in Morris 7800 C1 hepatoma cells. , 1993, The Biochemical journal.

[10]  R. Berge,et al.  On the mechanism of the hypolipidemic effect of sulfur-substituted hexadecanedioic acid (3-thiadicarboxylic acid) in normolipidemic rats. , 1993, Journal of lipid research.

[11]  J. Wijkander,et al.  An 100-kDa arachidonate-mobilizing phospholipase A2 in mouse spleen and the macrophage cell line J774. Purification, substrate interaction and phosphorylation by protein kinase C. , 1991, European journal of biochemistry.

[12]  A. Svardal,et al.  Fatty acid metabolism in liver of rats treated with hypolipidemic sulphur-substituted fatty acid analogues. , 1990, Biochimica et biophysica acta.

[13]  G. Gibbons.  Assembly and secretion of hepatic very-low-density lipoprotein. , 1990, The Biochemical journal.

[14]  I. Singh,et al.  Cellular oxidation of lignoceric acid is regulated by the subcellular localization of lignoceroyl-CoA ligases. , 1990, Journal of lipid research.

[15]  R. Berge,et al.  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 rats. , 1989, Biochemical pharmacology.

[16]  R. Berge,et al.  Alkylthioacetic acids (3-thia fatty acids) as non-beta-oxidizable fatty acid analogues: a new group of hypolipidemic drugs. III. Dissociation of cholesterol- and triglyceride-lowering effects and the induction of peroxisomal beta-oxidation. , 1989, Journal of lipid research.

[17]  R. Berge,et al.  Alkylthioacetic acid (3-thia fatty acids)--a new group of non-beta-oxidizable, peroxisome-inducing fatty acid analogues. I. A study on the structural requirements for proliferation of peroxisomes and mitochondria in rat liver. , 1989, Biochimica et biophysica acta.

[18]  A. Poulos,et al.  Distinct long chain and very long chain fatty acyl CoA synthetases in rat liver peroxisomes and microsomes. , 1988, Archives of biochemistry and biophysics.

[19]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[20]  H. Schulz,et al.  Beta-oxidation of unsaturated fatty acids: a revised pathway , 1987 .

[21]  E. Lied,et al.  Lipid digestion in cod (gadus morhua) , 1987 .

[22]  J. Hiltunen,et al.  beta-Oxidation of polyunsaturated fatty acids by rat liver peroxisomes. A role for 2,4-dienoyl-coenzyme A reductase in peroxisomal beta-oxidation. , 1986, The Journal of biological chemistry.

[23]  M. Connock,et al.  A sensitive spectrophotometric assay for peroxisomal acyl-CoA oxidase. , 1985, The Biochemical journal.

[24]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[25]  G. Mannaerts,et al.  Mitochondrial and peroxisomal fatty acid oxidation in liver homogenates and isolated hepatocytes from control and clofibrate-treated rats. , 1979, The Journal of biological chemistry.

[26]  W. Kunau,et al.  Degradation of Unsaturated Fatty Acids , 1978 .

[27]  W. Kunau,et al.  Degradation of unsaturated fatty acids. Identification of intermediates in the degradation of cis-4-decenoly-CoA by extracts of beef-liver mitochondria. , 1978, European journal of biochemistry.

[28]  M. Lopes-Virella,et al.  Cholesterol determination in high-density lipoproteins separated by three different methods. , 1977, Clinical chemistry.

[29]  P. Seglen.  Preparation of rat liver cells. 3. Enzymatic requirements for tissue dispersion. , 1973, Experimental cell research.

[30]  P. Seglen.  Preparation of rat liver cells. II. Effects of ions and chelators on tissue dispersion. , 1973, Experimental cell research.