ACAT2 contributes cholesteryl esters to newly secreted VLDL, whereas LCAT adds cholesteryl ester to LDL in mice.
The relative contributions of ACAT2 and LCAT to the cholesteryl ester (CE) content of VLDL and LDL were measured. ACAT2 deficiency led to a significant decrease in the percentage of CE (37.2 +/- 2.1% vs. 3.9 +/- 0.8%) in plasma VLDL, with a concomitant increase in the percentage of triglyceride (33.0 +/- 3.2% vs. 66.7 +/- 2.5%). Interestingly, the absence of 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 significantly increased 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-deficient mouse, whereas LDL was depleted in core lipids and enriched in surface lipids, appearing discoidal when observed by electron microscopy. We conclude that ACAT2 is important in the synthesis of VLDL CE, whereas LCAT is important in remodeling VLDL to LDL. Liver perfusions were performed, and perfusate apolipoprotein B accumulation rates in ACAT2-deficient mice were not significantly different from those of controls; perfusate VLDL CE decreased from 8.0 +/- 0.8% in controls to 0 +/- 0.7% in ACAT2-deficient mice. In conclusion, our data establish that ACAT2 provides core CE of newly secreted VLDL, whereas LCAT adds CE during LDL particle formation.
Lee
Richard G
RG
Arteriosclerosis Research Program, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Shah
Ramesh
R
Sawyer
Janet K
JK
Hamilton
Robert L
RL
Parks
John S
JS
Rudel
Lawrence L
LL
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D005838:Genotype; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D010477:Perfusion; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D000097587:Sterol O-Acyltransferase 2
D001055:Apolipoproteins B; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D010743:Phospholipids; D002785:Sterol O-Acyltransferase; D014280:Triglycerides; D000097587:Sterol O-Acyltransferase 2