Hepatic secretion of small lipoprotein particles in apobec-1-/- mice is regulated by the LDL receptor

Fatiha Nassir, Yan Xie, Bruce W. Patterson, Jianyang Luo, Nicholas O. Davidson

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Recent studies have examined the role of the LDL receptor (LDLR) in regulating murine hepatic lipoprotein production and apolipoprotein B (apoB) secretion, with divergent conclusions from in vivo versus in vitro approaches. We have re-examined this question, both in vivo and in vitro, using apobec-1-/- mice to model the pattern of human hepatic apoB-100 secretion. Hepatic triglyceride production in vivo (using Triton WR-1339) was unchanged in wild-type (WT) C57BL/6, apobec-1-/-, ldlr-/-, and [apobec-1-/-, ldlr-/-] mice, while apoB-100 production (using [35S]methionine incorporation) was increased >2-fold in [apobec-1-/-, ldlr-/-] mice. Although >90% of newly synthesized apoB floated within the d < 1.006 fraction of serum from all genotypes, fast-performance liquid chromatography separation revealed that nascent triglyceride-rich particles from [apobec-1-/-, ldlr-/-] mice, but not WT, apobec-1-/-, or ldlr -/- mice, distributed into smaller (intermediate and LDL-sized) particles. Studies in isolated hepatocytes from these different genotypes confirmed secretion of smaller particles exclusively from [apobec-1 -/-, ldlr-/-] mice, and pulse-chase analysis demonstrated increased secretion of apoB-100 with virtual elimination of posttranslational degradation. These results directly support the suggestion that the LDLR regulates hepatic apoB-100 production and modulates secretion of small, triglyceride-rich particles, both in vivo and in vitro.

Original languageEnglish
Pages (from-to)1649-1659
Number of pages11
JournalJournal of lipid research
Volume45
Issue number9
DOIs
StatePublished - Sep 2004

Keywords

  • Apolipoprotein B-100
  • Atherosclerosis
  • Lipoprotein biogenesis
  • VLDL secretion

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