Response of rhesus serum high density lipoproteins to cycles of diet-induced hypercholesterolemia.

Two male rhesus monkeys underwent cyclical feeding of a hypercholesterolemic diet (2% cholesterol, 25% coconut oil) and a low-fat Purina monkey chow diet. During the latter diet, high density lipoprotein (HDL) exhibited two components with peak densities of d = 1.081 g/ml and 1.109 g/ml named HDLL and HDLH, respectively. During the initial hypercholesterolemic stage, except for apo A-II which remained unchanged, there was a transient rise in HDL (mainly HDLL) as well as in HDL cholesterol and apo A-I, all reaching maximal values after about 2 weeks from the onset of the diet. The two HDL species changed neither in size nor density as compared to their baseline counterparts, but had a comparatively higher content in cholesteryl ester and lesser amounts of triglycerides and phospholipids as compared to the normocholesterolemic animal. With the development of overt hypercholesterolemia (plasma cholesterol levels above 400 mg/dl), both HDL particles increased in density due to the loss of surface components (phospholipids and unesterified cholesterol) and core triglycerides with only minor changes in protein and cholesteryl ester contents. At this stage, the same two animals exhibited significant changes in the size and buoyant density of LDL. When returned to a normal Purina chow diet, the animals' serum cholesterol levels declined rapidly to normal levels; normalization of the HDL distribution also occurred but at a comparatively later time (26 weeks). Our studies indicate that the two HDL subsets characteristic of the normocholesterolemic rhesus monkey undergo significant changes in buoyant density as a function of the stage of hypercholesterolemia and that changes in concentration and size mainly affect the HDLL subspecies. At levels of plasma cholesterol below 400 mg/dl, this cholesterol increment is reflected by a significant increase in the number of the HDL subspecies without the overt participation of the low density lipoprotein classes characteristic of the advanced hyperlipidemic stage. Since we previously reported that greatly increased levels of cholesteryl esters enriched low density lipoproteins, beta-VLDL (very low density lipoprotein) and pre-beta-VLDL during overt diet-induced hypercholesterolemia, it is apparent that cholesterol is distributed differently among lipoprotein particles containing either apo A-I, apo B, or apo E depending on its concentration in plasma.