出版社：American Society for Biochemistry and Molecular Biology
摘要：The relative contributions of ACAT2 and LCAT to the cholesterylester (CE) content of VLDL and LDL were measured. ACAT2 deficiencyled to a significant decrease in the percentage of CE (37.2± 2.1% vs. 3.9 ± 0.8%) in plasma VLDL, with aconcomitant increase in the percentage of triglyceride (33.0± 3.2% vs. 66.7 ± 2.5%). Interestingly, the absenceof ACAT2 had no apparent effect on the percentage CE in LDL,whereas LCAT deficiency significantly decreased the CE percentage(38.6 ± 4.0% vs. 54.6 ± 1.9%) and significantlyincreased the phospholipid percentage (11.2 ± 0.9% vs.19.3 ± 0.1%) of LDL. When both LCAT and ACAT2 were deficient,VLDL composition was similar to VLDL of the ACAT2-deficientmouse, whereas LDL was depleted in core lipids and enrichedin surface lipids, appearing discoidal when observed by electronmicroscopy. We conclude that ACAT2 is important in the synthesisof VLDL CE, whereas LCAT is important in remodeling VLDL toLDL. Liver perfusions were performed, and perfusate apolipoproteinB accumulation rates in ACAT2-deficient mice were not significantlydifferent from those of controls; perfusate VLDL CE decreasedfrom 8.0 ± 0.8% in controls to 0 ± 0.7% in ACAT2-deficientmice.
In conclusion, our data establish that ACAT2 provides core CEof newly secreted VLDL, whereas LCAT adds CE during LDL particleformation.Supplementary key words acyl-CoA:cholesterol acyltransferase 2 • lecithin:cholesterol acyltransferase • low density lipoprotein • very low density lipoprotein • hepatocyte • apolipoprotein B
