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Dietary fish oil-induced decrease in low density lipoprotein binding to fibroblasts is mediated by apolipoprotein E

V Linga1, M A Leight, L K Curtiss

  • 1Department of Comparative Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1040.

Journal of Lipid Research
|March 1, 1994
PubMed
Summary
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Fish oil (FO) diets reduced low-density lipoprotein (LDL) binding to skin fibroblasts by altering apolipoprotein E (apoE) content. This study investigated the roles of apoE and apolipoprotein B (apoB) in LDL binding, finding apoE significantly impacts this process.

Area of Science:

  • Lipid Metabolism
  • Cardiovascular Research
  • Biochemistry

Background:

  • Previous studies showed fish oil (FO) diets alter low-density lipoprotein (LDL) properties, reducing their binding affinity and cholesteryl ester accumulation in skin fibroblasts.
  • These alterations in FO LDL were linked to changes in apolipoprotein E (apoE) content, suggesting a role for apoE in impaired binding.

Purpose of the Study:

  • To test the hypothesis that FO LDL have reduced binding to skin fibroblasts due to decreased receptor-active apoE.
  • To determine the relative contributions of apoE and apolipoprotein B (apoB) in LDL binding to skin fibroblasts.

Main Methods:

  • Cynomolgus monkey LDL from lard or FO diets were isolated, characterized, and radioiodinated.
  • LDL binding assays were performed on skin fibroblasts in the presence of monoclonal antibodies against apoE or apoB-100.

Related Experiment Videos

  • Fluid phase precipitation assays were used to assess apoE and apoB epitope expression on LDL particles.

    • Main Results:

    • FO LDL were smaller, had lower apoE/apoB molar ratios (0.48 vs. 1.85), and weaker binding affinity (Kd = 11.3 vs. 3.8 μg/ml) compared to lard LDL.
    • Monoclonal antibody to apoB-100 (MB47) blocked 96% of FO LDL binding, while antibody to apoE (1D7) blocked only 23%.
    • Lard LDL binding was significantly inhibited by both MB47 (43%) and 1D7 (44%), with combined antibodies blocking all binding.

    Conclusions:

    • Reduced LDL binding to skin fibroblasts in FO-fed monkeys is primarily mediated by alterations in apoE content and receptor-binding activity.
    • ApoB-100 plays a dominant role in the binding of FO LDL, while apoE is crucial for lard LDL binding.
    • Dietary fat composition significantly influences LDL structure and function, impacting cellular interactions and potentially atherogenesis.