Abstract
Previous studies have indicated that LCAT may play a role in the generation of cholesteryl esters (CE) in plasma apolipoprotein B (apoB) lipoproteins. The purpose of the present study was to examine the quantitative importance of LCAT on apoB lipoprotein CE fatty acid (CEFA) composition. LCAT−/− mice were crossed into the LDL receptor (LDLr)−/− and apoE−/− background to retard the clearance and increase the concentration of apoB lipoprotein in plasma. Plasma free cholesterol was significantly elevated but total and esterified cholesterol concentrations were not significantly affected by removal of functioning LCAT in either the LDLr−/− or apoE−/− mice consuming a chow diet. However, when functional LCAT was removed from LDLr−/− mice, the CEFA ratio (saturated + monounsaturated/polyunsaturated) of plasma LDL increased 7-fold because of a 2-fold increase in saturated and monounsaturated CE, a 40% reduction in cholesteryl linoleate, and a complete absence of long chain (>18 carbon) polyunsaturated CE (20:4, 20:5n-3, and 22:6n-3), from 29.3% to 0%. Removal of functional LCAT from apoE−/− mice resulted in only a 1.6-fold increase in the CEFA ratio, due primarily to a complete elimination of long chain CE (7.7% to 0%). Our results demonstrate that LCAT contributes significantly to the CEFA pool of apoB lipoprotein and is the only source of plasma long chain polyunsaturated CE in these mice. —Furbee, J. W., Jr., O. Francone, and J. S. Parks. In vivo contribution of LCAT to apolipoprotein B lipoprotein cholesteryl esters in LDL receptor and apolipoprotein E knockout mice.
Highlights
Previous studies have indicated that LCAT may play a role in the generation of cholesteryl esters (CE) in plasma apolipoprotein B lipoproteins
When the LDLrϪ/Ϫ LCATϪ/Ϫ mice were compared with the LDLrϪ/Ϫ mice, there was no difference in total plasma cholesterol (TPC) concentrations, but there were significant increases in plasma free cholesterol (FC) (1.9-fold) and TGs (2.8-fold) concentrations
The purpose of the present study was to determine the quantitative importance of LCAT on apolipoprotein B (apoB) lipoprotein CE fatty acid (CEFA) composition using LDLrϪ/Ϫ and apoEϪ/Ϫ mice, two mouse models used extensively in atherosclerosis research
Summary
Previous studies have indicated that LCAT may play a role in the generation of cholesteryl esters (CE) in plasma apolipoprotein B (apoB) lipoproteins. Our results demonstrate that LCAT contributes significantly to the CEFA pool of apoB lipoprotein and is the only source of plasma long chain polyunsaturated CE in these mice.— Furbee, J. ACAT is an intracellular enzyme that uses fatty acyl-CoA and cholesterol as substrates for CE synthesis [1, 2]. LCAT is synthesized predominantly by the liver and secreted into plasma where it uses phosphatidylcholine (PC) and cholesterol in lipoprotein particles as substrate for CE synthesis [3, 4]. It has been hypothesized that LCAT is responsible for Abbreviations: apoA-I, apolipoprotein A-I; apoB, apolipoprotein B; apoE, apolipoprotein E; CE, cholesteryl ester(s); CEFA, cholesteryl ester fatty acid; EC, esterified cholesterol; FC, free cholesterol; HDL-C, HDL cholesterol; LDL-C, LDL cholesterol; LDLr, LDL receptor; PC, phosphatidylcholine; PL, phospholipid; POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine; TPC, total plasma cholesterol; VLDL-C, VLDL cholesterol.
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