Studies on rat liver phosphatidate phosphohydrolase and plasma lipids: Effect of HMG-CoA reductase inhibitors

Elisabet Humble, Ayman Al-Shurbaji, Erik Lund, Lars Berglund

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Normolipidemic rats were treated with HMG-CoA reductase inhibitors (lovastatin or pravastatin) for periods of 1-3 days. Administration of these drugs reduced plasma triacylglycerol levels. Lovastatin-treated rats displayed a 30% lower hepatic triacylglycerol secretion rate compared to controls as estimated using Triton WR-1339. Lovastatin in a dose of 0.1% in the diet for 3 days increased hepatic phosphatidate phosphohydrolase (PAP) activity 2- to 3-fold, both in the cytosolic and microsomal fractions. Similar effects were seen in the presence of 0.2% pravastatin. PAP in both fractions was stimulated to a lesser extent by treatment with 0.1% pravastatin. These differences in PAP activity obtained by different treatment regimens were preserved during purification of cytosolic PAP on hydroxylapatite. The increase in PAP activity upon treatment with lovastatin or pravastatin was gradual and occurred simultaneously with the apparent increase in HMG-CoA reductase activity. In rats treated with the reductase inhibitors, the activity of microsomal and cytosolic PAP was inversely correlated to plasma triacylglycerol levels. The results indicate that hepatic triacylglycerol and cholesterol synthesis might be co-ordinately regulated, and also suggest that the activity of PAP is rapidly modulated in concert with changes in plasma triacylglycerol levels.

Original languageEnglish (US)
Pages (from-to)32-38
Number of pages7
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume1214
Issue number1
DOIs
StatePublished - Aug 25 1994
Externally publishedYes

Keywords

  • HMG-CoA reductase
  • Lovastatin
  • Phosphatidate phosphohydrolase
  • Pravastatin
  • Triacylglycerol
  • VLDL

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Endocrinology

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