Hepatic apolipoprotein E expression promotes very low density lipoprotein-apolipoprotein B production in vivo in mice

J Lipid Res. 2000 Oct;41(10):1673-9.

Abstract

In addition to its role in the uptake of apolipoprotein B (apoB)-containing lipoproteins, apoE promotes hepatic very low density lipoprotein-triglyceride (VLDL-TG) production in animal models. However, it is not known if apoE increases the amount of TG per VLDL particle or the number of VLDL particles secreted. VLDL-apoB production is a measure of the rate of VLDL particle secretion. We determined the effects of apoE deficiency and apoE overexpression on VLDL-apoB production in mice. [(35)S]methionine was injected into endogenously label VLDL-apoB and Triton WR-1339 was simultaneously injected to block the catabolism of VLDL. Compared with wild-type mice, the VLDL-apoB production rate was decreased by 33% in apoE-deficient mice. Conversely, VLDL-apoB production was increased by 48% in mice overexpressing apoE compared with controls. Nascent VLDL, obtained from post-Triton plasma, had a decreased, not increased, content of TG per apoB in the apoE-overexpressing group compared with the control group. This study demonstrates that hepatic apoE expression increases the output of VLDL triglyceride by increasing the production rate of VLDL-apoB, suggesting that hepatic apoE influences the number of VLDL particles secreted by the liver.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apolipoproteins B / biosynthesis
  • Apolipoproteins B / drug effects*
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / metabolism
  • Apolipoproteins E / pharmacology*
  • Cholesterol / metabolism
  • Cholesterol Esters / metabolism
  • Female
  • Humans
  • Lipoproteins, VLDL / biosynthesis
  • Lipoproteins, VLDL / drug effects*
  • Lipoproteins, VLDL / metabolism
  • Liver / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Phospholipids / metabolism
  • Polyethylene Glycols / pharmacology
  • Triglycerides / metabolism

Substances

  • Apolipoproteins B
  • Apolipoproteins E
  • Cholesterol Esters
  • Lipoproteins, VLDL
  • Phospholipids
  • Triglycerides
  • Polyethylene Glycols
  • Cholesterol
  • tyloxapol