title: Stimulation of the in vivo production of very low density lipoproteins by apolipoprotein E is independent of the presence of the low density lipoprotein receptor.
abstract: Apolipoprotein (apo) E stimulates the secretion of very low density lipoproteins (VLDLs) by an as yet unknown mechanism. Recently, a working mechanism for apoE was proposed (Twisk, J., Gillian-Daniel, D. L., Tebon, A., Wang, L., Barrett, P. H., and Attie, A. D. (2000) J. Clin. Invest. 105, 521-532) in which apoE prevents the inhibitory action of the low density lipoprotein receptor (LDLr) by binding to it. We have first tested whether this newly described effect of the LDLr on VLDL secretion, obtained in vitro, is also observed in vivo. In LDLr knockout mice (LDLr-/-), the production of VLDL triglycerides and apoB was 30% higher than that in controls. Also the ratio of apoB100:apoB48 secretion was increased in the LDLr-/- mice. The composition of nascent VLDL was similar in both strains. To test whether the action of apoE depends on the presence of the LDLr, VLDL production was measured in LDLr-/- and apoE-/- LDLr-/- mice. Deletion of apoE on a LDLr-/- background still caused a 50% decrease of VLDL triglycerides and apoB production. The composition of nascent VLDL was again similar for both strains. We conclude that the effect of apoE on hepatic VLDL production is independent of the presence of the LDLr.
authors.affiliation: TNO Prevention and Health, Gaubius Laboratory, NL-2301 CE Leiden, The Netherlands. B.Teusink@pg.tno.nl
authors.forename: B
authors.initials: B
authors.lastname: Teusink
authors.forename: A R
authors.initials: AR
authors.lastname: Mensenkamp
authors.forename: H
authors.initials: H
authors.lastname: van der Boom
authors.forename: F
authors.initials: F
authors.lastname: Kuipers
authors.forename: K W
authors.initials: KW
authors.lastname: van Dijk
authors.forename: L M
authors.initials: LM
authors.lastname: Havekes
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D008079:Lipoproteins, VLDL / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL