DIETARY FATTY-ACID MODIFICATION OF HDL PHOSPHOLIPID MOLECULAR-SPECIESALTERS LECITHIN-CHOLESTEROL ACYLTRANSFERASE REACTIVITY IN CYNOMOLGUS MONKEYS

In the following report, cynomolgous monkeys, fed atherogenic diets co ntaining either saturated, monounsaturated, polyunsaturated (n-6 Poly) or fish oil (n-3 Poly) fat as 35% of total calories, provide a model for the study of dietary Eat effects on plasma lipoproteins and athero sclerosis. We have previously described the ability of polyunsaturated fat diets to lower plasma high density lipoprotein (HDL) cholesterol levels and alter HDL subpopulation distribution in the primate model. These experiments investigate possible mechanisms responsible for such modifications. Animals fed polyunsaturated fat had significantly lowe r plasma concentrations of HDL cholesterol, total plasma cholesterol, and apolipoprotein A-I, Such changes were reflected in the distributio n of protein among HDL subfractions, with the most remarkable modifica tion in subclass distribution being the preponderance of small HDL par ticles in the n-3 Poly-fed animals. Striking alterations were also obs erved in the distribu tion of phosphatidylcholine (PC) molecular speci es (diet effect P < 0.0001 for all major molecular species). Phosphati dylcholine isolated from lipoproteins were used to make recombinant HD L (rHDL) particles. The reaction rate of purified lecithin:cholesterol acyltransferase (LCAT) with particles made from n-3 Poly-derived PC w as 50% of that determined using rHDL formed with PC from other dietary groups (P < 0.0001). When the distribution of LCAT-derived rHDL chole steryl esters was analyzed, LCAT demonstrated little selectivity for c ertain PC molecular species except in n-3 Poly-derived rHDL where 18:2 -containing PC was selectively utilized. These data demonstrate that d ifferences in dietary fat intake can significantly alter HDL PC concen tration and molecular species distribution. We suggest that diet-induc ed alterations in HDL PC molecular species modify the type of choleste ryl esters produced during the LCAT reaction thereby affecting the pla sma cholesteryl ester pool. We also propose that dietary n-3 Poly affe cts cholesteryl ester metabolism in part via LCAT by lowering PC (LCAT substrate) availability altering the rate of the LCAT reaction, and d ecreasing HDL cholesterol concentrations; however, n-6 Poly dietary fa t effects on HDL concentration appear to be through some mechanism oth er than LCAT.