Effect of 3-thiadicarboxylic acid on lipid metabolism in experimental nephrosis

Ayman Al-Shurbaji, Jon Skorve, Rolf K. Berge, Mats Rudling, Ingemar Björkhem, Lars Berglund

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The effect of the sulfur-substituted fatty acid analogue 1,10 bis(carboxymethylthio)decane, also known as 3-thiadicarboxylic acid, on puromycin aminonucleoside-induced nephrotic hyperlipidemia was studied in rats. Treatment with 3-thiadicarboxylic acid (250 mg/kg) for 5 days reduced plasma levels of triglycerides from 5.8 to 2.7 mmol/L and cholesterol from 11.0 to 7.7 mmol/L. This was accounted for by decreases in very-low-density lipoprotein triglycerides, very-low-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, without any major changes in the composition of plasma lipoproteins. The activities of two enzymes involved in fatty acid synthesis (ATP:citrate lyase and fatty acid synthetase) were inhibited by 3-thiadicarboxylic acid treatment, whereas acetyl-coenzyme A carboxylase activity was unchanged. In contrast, treatment with the sulfur-substituted fatty acid analogue induced the peroxisomal β-oxidation of fatty acids ninefold and the mitochondrial β-oxidation by 54% to 73%, depending on the substrate used. This was accompanied by a 26% reduction in hepatic triglyceride secretion rate. The hepatic phosphatidate phosphohydrolase activity was unchanged. 3-Thiadicarboxylic acid treatment suppressed the activity of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, by 58%, whereas hepatic LDL receptor expression was unaltered. The activities of lipoprotein lipase and hepatic lipase were unchanged by treatment. These results demonstrated that treatment with 3-thiadicarboxylic acid ameliorates hyperlipidemia in experimental nephrosis primarily by decreasing the overproduction of very-low-density lipoprotein present. The data also indicate that hepatic very-low-density lipoprotein synthesis and secretion is strongly influenced by the availability of the fatty acid substrate under the same hyperlipidemic conditions.

Original languageEnglish (US)
Pages (from-to)1580-1586
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume13
Issue number11
StatePublished - 1993
Externally publishedYes

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Keywords

  • β-oxidation
  • 3-hydroxy-3-methylglutaryl-coenzyme A reductase
  • Cholesterol
  • Hypolipidemic drugs
  • Lipoprotein synthesis
  • Triacylglycerol

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Al-Shurbaji, A., Skorve, J., Berge, R. K., Rudling, M., Björkhem, I., & Berglund, L. (1993). Effect of 3-thiadicarboxylic acid on lipid metabolism in experimental nephrosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 13(11), 1580-1586.