DIETARY-FAT SATURATION MODIFIES THE METABOLISM OF LDL SUBFRACTIONS INGUINEA-PIGS

The effects of dietary fat saturation on the metabolism of low-density lipoprotein (LDL) subfractions were measured in adult male guinea pig s fed semipurified diets containing 15% (wt/wt) corn oil (CO; 58% lino leic acid), lard (24% palmitic/14% stearic acid), or palm kernel oil ( PK; 52% lauric/18% myristic acid). Animals fed the CO diet had lower p lasma total cholesterol levels than guinea pigs fed the PK or lard die ts (P<.01). Plasma LDL-1 (d = 1.019 to 1.05 g/mL) concentrations were 3.5- and 2.4-fold higher in animals fed the PK diet compared with the CO and lard groups, respectively, while LDL-2 (d = 1.05 to 1.09 g/mL) concentrations were not different among groups. For all dietary fat gr oups LDL-1 had a higher molecular weight and a larger diameter than LD L-2. LDL fractional catabolic rates (FCRs) varied, depending on both t he diet and the LDL subfraction. Animals fed the polyunsaturated CO di et had a more rapid LDL FCR than animals from the other two groups (P< .01). Within the same diet group, LDL-2 exhibited a slower turnover ra te than LDL-1 in animals fed the PK diet, while no differences in LDL subfraction FCR were found in the CO and lard groups. Animals fed the PK and lard diets did not exhibit significant modifications in the den sity distribution of LDL subfractions over a period of 33 hours. In co ntrast, animals fed the CO diet exhibited a shift of more buoyant to d enser LDL particles, suggesting that differences in LDL intravascular processing are mediated by dietary fat saturation. In vitro LDL bindin g to hepatic membranes confirmed the in vivo data with an increased ex pression of apolipoprotein B/E receptors (B(max)) in animals fed the C O diet (P<.02). Hepatic apolipoprotein B/E receptors exhibited less af finity for LDL-2 in the PK group, a result consistent with the less ra pid turnover of LDL-2 in PK-fed animals. The results suggest that diet ary fatty acids varying in saturation and composition have distinctive atherogenic potentials. The lowest plasma LDL cholesterol concentrati ons mediated by CO intake could in part be explained by induced change s in the composition and processing of LDL subfractions, resulting in faster LDL turnover rates in addition to increased expression of hepat ic apolipoprotein B/E receptors. Similarly, the hypercholesterolemic e ffects of the lard and PK diets appear to be related to differences in intravascular processing of LDL subfractions, with no interconversion between LDL-1 and LDL-2 and that is accompanied by decreased expressi on of hepatic apo B/E receptors. In addition, PK-fed guinea pigs exhib ited a decreased apolipoprotein B/E receptor affinity for LDL-2.