Oxidation affects the regulation of hepatic lipid synthesis by chylomicron remnants

Mariarosaria Napolitano, Roberto Rivabene, Michael Avella, Laura Amicone, Marco Tripodi, Kathleen M. Botham, Elena Bravo

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of native and oxidized chylomicron remnants on lipid synthesis in normal and oxidatively stressed liver cells were investigated using MET murine hepatocytes (MMH cells), a nontransformed mouse hepatocyte cell line that maintains a highly differentiated hepatic phenotype in culture. Lipid synthesis was determined by measuring the incorporation of [3H]oleate into cholesteryl ester, triacylglycerol, and phospholipid by the cells. The formation of cholesteryl ester and phospholipid was decreased by chylomicron remnants in a dose-dependent manner, while triacylglycerol synthesis was increased. Exposure of MMH cells to mild oxidative stress by incubation with CuSO4 (2.5 μM) for 24 h led to significantly increased incorporation of [3H]oleate into triacylglycerol and phospholipid, but not cholesteryl ester, in the absence of chylomicron remnants. In the presence of the lipoproteins, however, similar effects to those found in untreated cells were observed. Oxidatively modified chylomicron remnants prepared by incubation with CuSO4 (10 μM, 18 h, 37°C) did not influence cholesteryl ester or phospholipid synthesis in MMH cells, but had a similar effect to that found with native remnants on triacylglycerol synthesis. These findings show that hepatic lipid metabolism is altered by exposure to mild oxidative stress and by lipids from the diet delivered to the liver in chylomicron remnants, and these effects may play a role in the development of atherosclerosis.

Original languageEnglish
Pages (from-to)506-515
Number of pages10
JournalFree Radical Biology and Medicine
Volume30
Issue number5
DOIs
Publication statusPublished - Mar 1 2001

Keywords

  • Cholesterol esterification
  • Chylomicron remnants
  • Free radicals
  • Hepatocytes
  • Oxidative stress
  • Phospholipid synthesis
  • Triacylgylcerol synthesis

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

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