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J. Biol. Chem., Vol. 276, Issue 44, 40693-40697, November 2, 2001
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From the 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
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*
§,,
, and**
TNO Prevention and Health, Gaubius
Laboratory, NL-2301 CE Leiden, The Netherlands, ¶ Center for
Liver, Digestive and Metabolic Diseases, Laboratory of Pediatrics,
University Hospital Groningen, 9713 GZ Groningen, The Netherlands, and
Departments of Human and Clinical Genetics,
** Cardiology, and Internal
Medicine, Leiden University Medical Center, 2300 RA Leiden, The
Netherlands
/), 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.
*
This work was supported by Dutch Heart Foundation Grants NHS
96011 and 97067.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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