ABSTRACT
The effect of taurine on hypercholesterolemia induced by feeding a high-cholesterol (HC) diet (10g/kg) to rats was examined. When various amounts of taurine (0.25, 0.5, 1, 2.5, 5, 10, 20, 30, 40 or 50 g/kg diet) were supplemented to HC for 2 wk, serum total cholesterol gradually and significantly decreased in a dose-dependent manner and normalized at the dose of 10 g taurine/kg, compared with the control (cholesterol free) diet group. By contrast, serum HDL-cholesterol was elevated by taurine supplementation. The HC diet caused a significant decrease in the concentration of taurine in serum, liver and heart compared to that in the control group, and the effective dose of supplemental taurine to improve its reduction was 2.5 g/kg diet. In the hypercholesterolemic rats fed the HC diet, the excretion of fecal bile acids and hepatic cholesterol 7 alpha-hydroxylase (CYP7A1) activity and its mRNA level increased significantly, and the supplementation of taurine further enhanced these indexes, indicating an increase in cholesterol degradation. The abundance of mRNA for Apo A-I, one of the main components of HDL, was reduced by HC and recovered by taurine supplementation. Agarose gel electrophoresis revealed that, in hypercholesterolemic rats fed the HC diet, the serum level of the heavier VLDL increased significantly, but taurine repressed this increase and normalized this pattern. Significant correlations were observed between the time- and dose-dependent increases of CYP7A1 gene expression and the decrease of blood cholesterol concentration in rats fed the HC diet supplemented with taurine (time, r = -0.538, P < 0.01, n = 32; dose, r = -0.738, P < 0.001, n = 20). These results suggest that the hypocholesterolemic effects of taurine observed in the hypocholesterolemic rats fed the HC diet were mainly due to the enhancement of cholesterol degradation and the excretion of bile acid.
Subject(s)
Cholesterol, Dietary/administration & dosage , Cholesterol/metabolism , Liver/metabolism , Taurine/pharmacology , Animals , Body Weight/drug effects , Cholesterol/blood , Cholesterol 7-alpha-Hydroxylase/genetics , Cholesterol 7-alpha-Hydroxylase/metabolism , Cholesterol, Dietary/metabolism , Dose-Response Relationship, Drug , Eating/drug effects , Hypercholesterolemia/etiology , Hypercholesterolemia/metabolism , Lipoproteins/blood , Male , Organ Size/drug effects , RNA, Messenger/blood , Rats , Rats, WistarABSTRACT
The induction of malic enzyme gene expression by triiodothyronine and insulin was severely blunted in rat monolayer hepatocytes cultured on type I collagen compared with that in spherical hepatocytes cultured on a reconstituted basement membrane gel (EHS-gel). Although the mRNA level of thyroid hormone receptor beta (TR beta) gradually decreased in the monolayer hepatocytes during culture, the mRNA level in the hepatocytes on EHS-gel was maintained at around the in vivo level. Our results suggest that the maintenance of TR beta mRNA on EHS-gel is responsible for the high responsiveness to thyroid hormone in a hepatocyte culture.