Effect of a high fat/cholesterol diet with or without eicosapentaenoic acid on plasma lipids, lipoproteins and lipid transfer protein activity in the marmoset.

ABSTRACT

Marmosets fed a diet supplemented with 0.2% cholesterol and 10% sheep fat (by weight) developed hypercholesterolemia with a 4-fold increase in plasma cholesterol (4.28 +/- 0.57-16.38 +/- 4.22 mmol/l, mean +/- SD, P less than 0.001). This was due mainly to a 5-fold increase in the intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) fraction (d = 1.006-1.063 g/ml). The proportion of plasma cholesterol in high density lipoproteins (HDL) decreased from 56% to 25% although HDL cholesterol increased from 2.40 +/- 0.42 to 4.09 +/- 0.92 mmol/l (P less than 0.001), and HDL particle radius increased from 5.10 +/- 0.18 nm to 6.06 +/- 0.73 nm (P less than 0.05). Plasma lipid transfer protein (LTP) activity increased 2.5-fold in whole plasma and 2-fold in lipoprotein-deficient plasma. The atherogenic lipoprotein profile was attenuated by adding 0.8% eicosapentaenoic acid (EPA, 205 n - 3, as the ethyl ester) to the atherogenic diet. Plasma cholesterol increased only 55% to 6.64 +/- 2.55 mmol/l with only an 80% increase in lipoproteins in the d = 1.006-1.063 g/ml fraction and a more favourable proportion of plasma cholesterol in HDL (44%) than without EPA. LTP activity was reduced to 1.7-fold above control in whole plasma by addition of EPA to the atherogenic diet. There was a positive correlation between plasma cholesterol and LTP activity in whole plasma (r = 0.89, P less than 0.001) and in lipoprotein-deficient plasma (r = 0.67, P less than 0.001). EPA therefore attenuated some of the adverse effects of a 0.2% cholesterol, 10% sheep fat diet on plasma lipids and lipoproteins and induced a less atherogenic profile.