CARBOHYDRATE-FAT EXCHANGE AND REGULATION OF HEPATIC CHOLESTEROL AND PLASMA-LIPOPROTEIN METABOLISM IN THE GUINEA-PIG

Adult female guinea pigs were fed semipurified diets containing increasing concentrations of saturated fat (2.5%, 7.5%, 15%, and 25% wt/wt) to determine effects of exchanging fat-carbohydrate calories on lipoprotein metabolism. Plasma very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) did not vary but plasma low-density lipoprotein (LDL) concentrations increased with increasing fat calories. LDL cholesterol values were 42+/-26, 61+/-17, 92+/-25, and 98+/-21 mg/dL (mean+/-SD, n=5), respectively. The relative proportion of cholesterol ester increased and triacylglycerol (TAG) decreased for VLDL, LDL, and HDL as dietary fat increased. Plasma lecithin cholesterol acyltransferase (LCAT) activity was positively correlated with HDL cholesterol ester content. Hepatic cholesterol and TAG concentrations were highest in animals fed 25% fat (P<.01). Hepatic apolipoprotein (apo)B/E receptor maximal binding capacity (Bmax) was 30% higher in animals fed 2.5% and 7.5% fat as compared with those fed 15% and 25% fat (P<.01) and inversely correlated with plasma LDL (r=-.85,P<.01). In contrast, HDL binding to guinea pig hepatic membranes exhibited a significant positive correlation with dietary fat quantity (r=.98,P<.001), consistent with a dose-response with increasing fat calories. The activity of hepatic 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase was not affected by the amount of dietary fat, whereas the activity of acyl and ACAT activity exhibited a positive correlation for all dietary groups (r=.75,P<.001) these results demonstrate that exchange of saturated dietary fat for carbohydrate calories results in significant modifications in the regulation of metabolic pathways that determine plasma LDL concentrations and hepatic cholesterol homeostasis.