RESUMEN
The regulating process of cholesterol in the liver was studied in relation to its exogenous contribution in the rats fed high-fat (28%) high-cholesterol (1.2%) diets rich in saturated (S) fat (lard) or polyunsaturated (PU) fat (corn oil). Accordingly, the fate of 14C free cholesterol originating from high- or low-density lipoproteins (LDL) was examined in the biliary, hepatic and plasmatic lipids, as well as the activity of two key enzymes in the metabolism of lipoproteins: lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT). The LPL activity increased in the S diet, in comparison to the PU diet or to a low fat (6%) control (C) diet and the LCAT activity increased but not significantly in the PU diet. In bile the secretion of 14C-cholesterol and 14C-bile salts originating from 14C-cholesterol-HDL increased in the S diet compared to the PU diet and a C diet [previous results]. S and PU diets increased to the same extent the hepatic storage of 14C-esterified cholesterol originating from LDL, compared to the C diet. This cholesterol would contribute to a greater extent to the hepatic synthesis of the lipoproteins destined for the plasma in the case of the S diet than that of PU diet. These results may be explained by the adaptation of hepatic acyl cholesterol acyl transferase and cholesterolesterase to both high-fat-diet enzymes acting simultaneously on the two free and esterified cholesterol compartments. It resulted in an important redistribution of the cholesterol of these two compartments between plasma, bile and liver.
Asunto(s)
Colesterol/metabolismo , Grasas de la Dieta/administración & dosificación , Lipoproteínas HDL/análisis , Lipoproteínas LDL/análisis , Animales , Bilis/metabolismo , Colesterol en la Dieta/metabolismo , HDL-Colesterol/metabolismo , Grasas de la Dieta/farmacología , Lipoproteína Lipasa/metabolismo , Liposomas/metabolismo , Hígado/enzimología , Hígado/metabolismo , Masculino , Fosfatidilcolina-Esterol O-Aciltransferasa/metabolismo , Ratas , Ratas EndogámicasRESUMEN
In order to study the relationship between bile cholesterol and free cholesterol carried by high and low density lipoproteins (HDL and LDL), 10 male Wistar rats, 11 weeks old and fed with a standard diet were divided into 3 groups which received an intravenous infusion (jugular vein) of either LDL, HDL or liposomes. Liposomes were used for comparison because they are assimilated by hepatocytes, but are not recognized by specific receptors. HDL isolated from rat sera were labeled with [14C]cholesterol by molecular exchange and LDL were labeled by exchange with [14C]cholesterol incorporated into phosphatidyl choline/cholesterol liposomes. The peaks of radioactivity appeared in bile 30 min after the HDL or liposome injection and after 210 min for the LDL injection. The kinetic behavior of the cholesterol carried by the liposomes was quite similar to that of cholesterol carried by HDL. Cholesterol carried by HDL was metabolized in bile salts faster than that carried by LDL: cholesterol-HDL or cholesterol-liposomes contributed to the same extent to the secretion of bile cholesterol (15 and 11%, respectively, of the injected dose), LDL (20% of the injected dose). However, the main part of [14C]cholesterol from HDL, LDL or liposomes was metabolized in bile salts. Thus, cholesterol from an exogenous source seemed to be used mainly as a substrate for bile salts. Our study revealed a difference between the hepatic metabolism of HDL, liposomes and LDL in the rat: the kinetic difference between the secretions of the radioactive compounds in bile may be explained by differences in assimilation, intracellular pathways or bile secretion.