On the interrelationship between hepatic carnitine, fatty acid oxidation, and triglyceride biosynthesis in nephrosis

Ayman Al-Shurbaji, Lars Berglund, Rolf K. Berge, Gitten Cederblad, Elisabet Humble

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The nephrotic syndrome is associated with disturbances in plasma lipid pattern and metabolism. However, the reason for these perturbations is poorly understood. In the present study, we have investigated hepatic triglyceride metabolism in puromycin aminonucleoside-induced nephrotic syndrome in rats. Nephrotic rats displayed a 70% increase in hepatic triglyceride levels compared to controls (16.9±1.6 vs. 9.8±0.6 μmol/g liver; means±SEM, P<0.01). The capacity for hepatic mitochondrial β-oxidation of fatty acids was substantially elevated (80%). This was associated with a rise in the liver content of the fatty acid carrier carnitine (1.24±0.06 vs. 0.85±0.07 μmol/g dry weight, P<0.05). A positive correlation between the levels of acetylcarnitine and acetyl-CoA was found in normal as well as in nephrotic rats, implying that carnitine plays an important role as an acetyl group acceptor in the liver under normo- and hyperlipidemic conditions. Changes in carnitine levels seem to be tightly coupled to the rate of fatty acid oxidation. There was a significant elevation in the activity of phosphatidate phosphohydrolase (E.C. 3.1.3.4) in liver microsomes from nephrotic rats (1.07±0.09 vs. 0.81±0.04 nmol/min·mg protein, P<0.02). Hepatic very low density lipoprotein (VLDL)-triglyceride secretion rate was 18% higher in nephrotic rats than in controls. The results demonstrate a deranged hepatic triglyceride metabolism in nephrosis, with an increased hepatic triglyceride biosynthesis, a sizable accumulation of hepatic triglycerides, and only a modest increase in VLDL triglyceride secretion. In addition, mitochondrial β-oxidation of fatty acids was enhanced, associated with an increased availability of carnitine.

Original languageEnglish (US)
Pages (from-to)847-852
Number of pages6
JournalLipids
Volume32
Issue number8
DOIs
StatePublished - Aug 1997
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Food Science
  • Biochemistry

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