RESUMEN
To test the effects of exchanging dietary complex and simple carbohydrate for fat calories on lipoprotein metabolism, guinea pigs were fed two different fat/carbohydrate ratios: 2.5:58% (w/w) or 25:29% (w/w) with either sucrose or starch as the carbohydrate source. Animals fed high-fat had higher plasma low-density lipoprotein (LDL) and hepatic cholesterol concentrations than animals fed low-fat diets (P < 0.01). The cholesteryl ester content per particle was higher, and the number of triacylglycerol (TAG) molecules was lower in very low density lipoprotein (VLDL) and LDL from animals fed high-fat diets. Intake of high-fat/sucrose resulted in higher plasma LDL concentrations than intake of high-fat/starch, and animals fed low-fat/starch had the highest plasma TAG concentrations associated with VLDL particles containing more TAG molecules, as well as a TAG-enriched LDL. The activity of plasma lecithin cholesteryl:acyl transferase (LCAT) was highest in animals fed high-fat/sucrose, and heart lipoprotein lipase (LPL) activity was higher in animals fed high-fat diets. Hepatic apoprotein B/E (apo B/E) receptor number (Bmax) was increased 21% with low-fat diets (P < 0.01). These results suggest that the hypercholesterolemia induced by high-fat and by sucrose intake are associated with a higher plasma LCAT activity which results in a cholesteryl ester-enriched VLDL which, by the action of LPL, might be more readily converted to LDL through the delipidation cascade leading to downregulation of hepatic apo B/E receptors. The hypertriglyceridemia associated with low-fat intake may result from increased production of VLDL TAG, which would explain the increased TAG content and the higher TAG/CE ratio of VLDL from animals fed the low-fat/starch diet.
Asunto(s)
Carbohidratos de la Dieta/farmacología , Lipoproteínas/sangre , Animales , Apolipoproteínas B/sangre , Colesterol/sangre , Ésteres del Colesterol/sangre , Ésteres del Colesterol/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Ingestión de Energía , Cobayas , Lipoproteína Lipasa/metabolismo , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , Hígado/metabolismo , Masculino , Miocardio/enzimología , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Receptores de LDL/metabolismo , Almidón/administración & dosificación , Sacarosa/administración & dosificación , Triglicéridos/sangreRESUMEN
Male Hartley guinea pigs were fed semipurified diets containing various levels of psyllium and cholesterol to determine mechanisms by which psyllium lowers plasma low density lipoprotein (LDL) concentrations. Four diets were tested: control diets with 12.5% (w/w) cellulose, and psyllium diets in which cellulose was partially replaced with 7.5% (w/w) psyllium. Two levels of dietary cholesterol were used, either low (LC, 0.04%, w/w) or high (HC, 0.25%, w/w). Plasma LDL was reduced by 30 and 54% with psyllium intake in the LC and HC groups, respectively (P < 0.001), while plasma very low density lipoprotein (VLDL) was lowered only in the HC group (P < 0.001). Psyllium intake modified LDL composition and size compared to LDL from control animals with a lower proportion of cholesteryl ester and higher proportion of triacylglycerol, lower molecular weight, smaller diameter, and higher peak density (P < 0.001). Plasma VLDL from animals fed the psyllium-HC diet compared to the control-HC contained lower relative proportions of free and esterified cholesterol and a higher proportion of triacylglycerol, compositional characteristics similar to VLDL from animals fed LC diets. Hepatic free and esterified cholesterol concentrations were significantly reduced by psyllium an average of 25 and 55%, respectively, while hepatic HMG-CoA reductase activity was increased in both psyllium groups compared to the respective controls (P < 0.001). In addition, psyllium intake reduced hepatic acyl-CoA:cholesterol acyltransferase (ACAT) activity in both the LC and HC groups (P < 0.001) and increased hepatic membrane apoB/E receptor number (Bmax) by 17 and 52% for animals fed LC and HC diets, respectively (P < 0.005). Significant psyllium-induced increases in cholesterol 7 alpha-hydroxylase of 4- and 1.6-fold were also observed in animals fed the LC and HC diets respectively (P < 0.001). These results indicate that psyllium generates a negative cholesterol balance across the liver which results in induction of cholesterol 7 alpha-hydroxylase and HMG-CoA reductase and suppression of ACAT activities, upregulation of apoB/E receptors, and secretion of smaller VLDL particles, metabolic alterations that contribute to a lowering of plasma LDL cholesterol levels.