Normal production rate of apolipoprotein B in LDL receptor-deficient mice.
The low density lipoprotein (LDL) receptor is well known for its role in mediating the removal of apolipoprotein B (apoB)-containing lipoproteins from plasma. Results from in vitro studies in primary mouse hepatocytes suggest that the LDL receptor may also have a role in the regulation of very low density lipoprotein (VLDL) production. We conducted in vivo experiments using LDLR-/-, LDLR+/-, and wild-type mice (LDLR indicates LDL receptor gene) in which the production rate of VLDL was measured after the injection of [35S]methionine and the lipase inhibitor Triton WR1339. Despite the fact that LDLR-/- mice had a 3.7-fold higher total cholesterol level and a 2.1-fold higher triglyceride level than those of the wild-type mice, there was no difference in the production rate of VLDL triglyceride or VLDL apoB between these groups of animals. Experiments were also conducted in apobec1-/- mice, which make only apoB-100, the form of apoB that binds to the LDL receptor. Interestingly, the apobec1-/- mice had a significantly higher production rate of apoB than did the wild-type mice. However, despite significant differences in total cholesterol and triglyceride levels, there was no difference in the production rate of total or VLDL triglyceride or VLDL apoB between LDLR-/- and LDLR+/- mice on an apobec1-/- background. These results indicate that the LDL receptor has no effect on the production rate of VLDL triglyceride or apoB in vivo in mice.
Millar
John S
JS
Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA. jsmillar@mail.med.upenn.edu
Maugeais
Cyrille
C
Fuki
Ilia V
IV
Rader
Daniel J
DJ
D000071479:APOBEC-1 Deaminase; D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis* / Q000097:blood; D003564:Cytidine Deaminase; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007275:Injections, Intravenous; D008049:Lipase / Q000037:antagonists & inhibitors; D008079:Lipoproteins, VLDL / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency* / Q000502:physiology; D014280:Triglycerides / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism
D001055:Apolipoproteins B; D004791:Enzyme Inhibitors; D008079:Lipoproteins, VLDL; D016601:RNA-Binding Proteins; D011973:Receptors, LDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D011092:Polyethylene Glycols; D008049:Lipase; D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase; C016811:tyloxapol