Hepatic apolipoprotein E expression promotes very low density lipoprotein-apolipoprotein B production in vivo in mice.
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.
Maugeais
C
C
Department of Medicine, University of Pennsylvania Health System, Philadelphia, PA 19104, USA.
Tietge
U J
UJ
Tsukamoto
K
K
Glick
J M
JM
Rader
D J
DJ
D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000187:drug effects*; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D005260:Female; D006801:Humans; D008079:Lipoproteins, VLDL / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010743:Phospholipids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008079:Lipoproteins, VLDL; D010743:Phospholipids; D014280:Triglycerides; D011092:Polyethylene Glycols; D002784:Cholesterol; C016811:tyloxapol