LDL Cholesteryl Oleate

Abstract

Cholesteryl esters (CE) are synthesized by 2 enzymes, lecithin:cholesterol acyltransferase (LCAT) and acylCoA:cholesterol acyltransferase (ACAT). LCAT functions in the plasma and forms CE in HDL by transferring polyunsaturated fatty acid from phosphatidylcholine to cholesterol. ACAT, which functions intracellularly, uses fatty acid from acylCoA and forms CE enriched in monounsaturated fatty acid. Two isoforms of ACAT are expressed.1 ACAT1 is present in many tissues and produces the CE that are stored intracellularly, whereas ACAT2 is expressed in the intestine and liver and produces the CE that are secreted in chylomicrons and VLDL.2 See page 1396 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , Bell et al report that ACAT2 gene deletion prevents hypercholesterolemia and atherosclerosis induced by diets containing 10% saturated or monounsaturated fat in a murine model of high LDL apoB100 only, LDL receptor-deleted (LDLr−/−) mice.3 These mice also had larger LDL particle size and hypertriglyceridemia. They attribute the protection of ACAT2 deficiency to a decrease in LDL particles enriched in CE derived from oleate (monounsaturated). When the diet contains large amounts of monounsaturated fats, ACAT2 activity appears to favor production of VLDL particles containing an excessive amount of cholesteryl oleate,4 and these monounsaturated CE remain associated with the lipoprotein particle when it undergoes conversion to LDL. These findings remind us that CE synthesized in the liver can be a source of CE for LDL, a fact that tends to be overlooked because of the current emphasis on the role of the reverse cholesterol transport pathway and cholesteryl ester transport protein (CETP) in supplying CE to VLDL and ultimately LDL. The Figure illustrates how LCAT, CETP, and ACAT2 function to supply monounsaturated and polyunsaturated CE that can accumulate in LDL. A schematic summary of the pathways that provide cholesteryl esters (CE) for incorporation …