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ACAT inhibitors decrease secretion of cholesteryl esters and apolipoprotein B by perfused livers of African green
T P Carr1, R L Hamilton, L L Rudel
1Department of Comparative Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157.
Journal of Lipid Research
|January 1, 1995
Summary
Newly synthesized cholesteryl esters are crucial for the assembly and secretion of hepatic lipoproteins, particularly apoB-containing particles. ACAT inhibitors reduced cholesteryl ester and apoB secretion, suggesting coordinated regulation in lipoprotein production.
Area of Science:
- Lipid metabolism
- Hepatology
- Biochemistry
Background:
- Hepatic lipoprotein assembly and secretion are vital processes for lipid transport.
- Cholesteryl esters are key components of lipoproteins, but their precise role in secretion is debated.
Purpose of the Study:
- To investigate the role of newly synthesized cholesteryl esters in hepatic lipoprotein assembly and secretion.
- To determine if ACAT (acyl-CoA:cholesterol acyltransferase) inhibition affects the secretion of specific lipids and apolipoproteins.
Main Methods:
- Perfusion of isolated African green monkey livers with medium containing one of three ACAT inhibitors (CI-976, CP-113818, or PD-138142-15).
- Measurement of secreted lipids (cholesteryl ester, triacylglycerol) and apolipoproteins (apoB, apoA-I, apoA-II, apoE).
Main Results:
- All three ACAT inhibitors significantly decreased cholesteryl ester and apoB secretion.
- Triacylglycerol secretion was reduced by two inhibitors but not the third, indicating variable effects.
- A strong positive correlation was observed between the inhibition of cholesteryl ester and apoB secretion across all inhibitors.
Conclusions:
- Newly synthesized cholesteryl esters appear to be essential for the assembly and secretion of hepatic apoB-containing lipoproteins.
- Cholesteryl ester and apoB secretion are coordinately regulated.
- Triacylglycerol plays a role in lipoprotein assembly, but it is distinct from the role of cholesteryl ester.