On the mechanism of the hypolipidemic effect of sulfur-substituted hexadecanedioic acid (3-thiadicarboxylic acid) in normolipidemic rats

J. Skorve, A. Al-Shurbaji, D. Asiedu, I. Bjorkhem, Lars Berglund, R. K. Berge

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The mechanism behind the hypolipidemic effect of the sulfur-substituted non-β-oxidizable fatty acid analogue 1,10 bis(carboxymethylthio)decane, also known as 3-thiadicarboxylic acid, was studied in normolipidemic rats. Treatment with 3-thiadicarboxylic acid markedly decreased plasma levels of free fatty acids, triglycerides, and cholesterol. This was accompanied by a corresponding reduction in very low density lipoprotein (VLDL)-triglyceride and low density lipoprotein (LDL)-cholesterol levels (by 46% and 42%, respectively), whereas the decrease in high density lipoprotein (HDL)- cholesterol levels was less pronounced (16%). However, the composition of the various plasma lipoprotein fractions was essentially unchanged. Fatty acid oxidation in both mitochondria and peroxisomes was stimulated in parallel; the activities of ATP:citrate lyase and fatty acid synthase, two key enzymes in fatty acid synthesis, were inhibited. Hepatic triglyceride biosynthesis was retarded, as indicated by a decrease in the liver triglyceride content along with a 30% reduction of hepatic VLDL-triglyceride secretion. This was accompanied by a 50% inhibition of phosphatidate phosphohydrolase. The activities of plasma lipoprotein lipase as well as hepatic lipase were somewhat higher (18%) in treated animals, suggesting a slight increase in the clearance potential of triglyceride-rich lipoproteins. The cholesterol- lowering effect was accompanied by a considerable reduction (75%) in HMG-CoA reductase activity and a less pronounced inhibition of cholesterol 7 α- hydroxylase (52%), and acyl-CoA:cholesterol acyltransferase (25%) activities. The present data suggest that the hypotriglyceridemic and hypocholesterolemic properties of sulfur-substituted fatty acid analogues are primarily due to effects on triglyceride and cholesterol synthesis.

Original languageEnglish (US)
Pages (from-to)1177-1185
Number of pages9
JournalJournal of Lipid Research
Volume34
Issue number7
StatePublished - 1993
Externally publishedYes

Fingerprint

Sulfur
Rats
Triglycerides
Fatty Acids
Liver
Cholesterol
Plasmas
Lipoproteins
ATP Citrate (pro-S)-Lyase
Phosphatidate Phosphatase
Cholesterol 7-alpha-Hydroxylase
Sterol O-Acyltransferase
Hydroxymethylglutaryl CoA Reductases
Fatty Acid Synthases
Mitochondria
Peroxisomes
Lipoprotein Lipase
Biosynthesis
Lipase
Nonesterified Fatty Acids

Keywords

  • ACAT
  • cholesterol 7 α-hydroxylase
  • hepatic lipase
  • HMG-CoA reductase
  • hypolipidemic drug
  • lipogenic enzymes
  • lipoprotein composition
  • lipoprotein lipase
  • plasma lipids
  • triglyceride and cholesterol synthesis

ASJC Scopus subject areas

  • Endocrinology

Cite this

On the mechanism of the hypolipidemic effect of sulfur-substituted hexadecanedioic acid (3-thiadicarboxylic acid) in normolipidemic rats. / Skorve, J.; Al-Shurbaji, A.; Asiedu, D.; Bjorkhem, I.; Berglund, Lars; Berge, R. K.

In: Journal of Lipid Research, Vol. 34, No. 7, 1993, p. 1177-1185.

Research output: Contribution to journalArticle

Skorve, J. ; Al-Shurbaji, A. ; Asiedu, D. ; Bjorkhem, I. ; Berglund, Lars ; Berge, R. K. / On the mechanism of the hypolipidemic effect of sulfur-substituted hexadecanedioic acid (3-thiadicarboxylic acid) in normolipidemic rats. In: Journal of Lipid Research. 1993 ; Vol. 34, No. 7. pp. 1177-1185.
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AU - Berglund, Lars

AU - Berge, R. K.

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