VLDL lipolysis products increase VLDL fluidity and convert apolipoprotein E4 into a more expanded conformation

Sarada D. Tetali, Madhu S. Budamagunta, Catalina Simion, Laura J. Den Hartigh, Tamás Kálai, Kálmán Hideg, Danny M. Hatters, Karl H. Weisgraber, John C Voss, John C Rutledge

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Our previous work indicated that apolipoprotein (apo) E4 assumes a more expanded conformation in the postprandial period. The postprandial state is characterized by increased VLDL lipolysis. In this article, we tested the hypothesis that VLDL lipolysis products increase VLDL particle fluidity, which mediates expansion of apoE4 on the VLDL particle. Plasma from healthy subjects was collected before and after a moderately high-fat meal and incubated with nitroxyl-spin labeled apoE. ApoE conformation was examined by electron paramagnetic resonance spectroscopy using targeted spin probes on cysteines introduced in the N-terminal (S76C) and C-terminal (A241C) domains. Further, we synthesized a novel nitroxyl spin-labeled cholesterol analog, which gave insight into lipoprotein particle fluidity. Our data revealed that the order of lipoprotein fluidity was HDL∼LDL<VLDL<VLDL+lipoprotein lipase. Moreover, the conformation of apoE4 depended on the lipoprotein fraction: VLDL-associated apoE4 had a more linear conformation than apoE4 associated with LDL or HDL. Further, by changing VLDL fluidity, VLDL lipolysis products significantly altered apoE4 into a more expanded conformation. Our studies indicate that after every meal, VLDL fluidity is increased causing apoE4 associated with VLDL to assume a more expanded conformation, potentially enhancing the pathogenicity of apoE4 in vascular tissue.

Original languageEnglish (US)
Pages (from-to)1273-1283
Number of pages11
JournalJournal of Lipid Research
Volume51
Issue number6
DOIs
StatePublished - Jun 1 2010

Keywords

  • Lipid fluidity
  • Postprandial state
  • Structural conformation
  • Very low density lipoprotein

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

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    Tetali, S. D., Budamagunta, M. S., Simion, C., Den Hartigh, L. J., Kálai, T., Hideg, K., Hatters, D. M., Weisgraber, K. H., Voss, J. C., & Rutledge, J. C. (2010). VLDL lipolysis products increase VLDL fluidity and convert apolipoprotein E4 into a more expanded conformation. Journal of Lipid Research, 51(6), 1273-1283. https://doi.org/10.1194/jlr.M000406