Regulation of hepatic 7 alpha-hydroxylase expression by dietary psyllium in the hamster.

Abstract

Soluble fiber consistently lowers plasma total and low density lipoprotein (LDL)-cholesterol concentrations in humans and various animal models including the hamster; however, the mechanism of this effect remains incompletely defined. We performed studies to determine the activity of dietary psyllium on hepatic 7a-hydroxylase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and LDL receptor expression in the hamster. In animals fed a cholesterol-free semisynthetic diet containing 7.5% cellulose (avicel) as a fiber source, substitution of psyllium for avicel increased hepatic 7a-hydroxylase activity and mRNA levels by 34-fold. Comparable effects on 7a-hydroxylase expression were observed with 1% cholestyramine. Psyllium also increased hepatic 7a-hydroxylase activity and mRNA in animals fed a diet enriched with cholesterol and triglyceride. Activation of 7a-hydroxylase was associated with an increase in hepatic cholesterol synthesis that was apparently not fully compensatory since the cholesterol content of the liver declined. Although dietary psyllium did not increase hepatic LDL receptor expression in animals fed the cholesterol-free, very-low-fat diet, it did increase (or at least restore) receptor expression that had been downregulated by dietary cholesterol and triglyceride. Thus, 7.5% dietary psyllium produced effects on hepatic 7a-hydroxylase and LDL metabolism that were similar to those of 1% cholestyramine. Induction of hepatic 7a-hydroxylase activity by dietary psyllium may account, in large part, for the hypocholesterolemic effect of this soluble fiber. (J.

Influência de frações da parede celular de levedura (Saccharomyces cerevisiae) sobre os índices séricos de glicose e lipídios, microbiota intestinal e produção de ácidos graxos voláteis (AGV) de cadeias curtas de ratos em crescimento

“…HORTON et al 23 verificaram, em experimentos realizados com hamsters, um efeito hipocolesterolêmico pela adição de 7,5% de psilium (fibra solúvel) à ração. Os autores atribuíram este efeito ao aumento da atividade da enzima 7α-hidroxilase, que é similar àquele produzido pela presença de 1% de colesteramina.…”

Kinetic parameters for high density lipoprotein apoprotein AI and cholesteryl ester transport in the hamster.

“…The hamster appears to be an excellent model for the study of HDL metabolism and reverse cholesterol transport. Serum HDL levels respond to dietary factors in a similar manner in hamsters (14,15, and L.A. Woollett and D.K. Spady, unpublished observations) and humans (3,16,17).…”

“…Rates of LDL cholesterol uptake were measured using primed infusions of [ 125 I]tyramine cellobiose-labeled homologous LDL as described previously (15). The molar ratio of tyramine cellobiose to apo B was ‫ف‬ 1 and the specific activity of the radiolabeled LDL preparations equaled ‫ف‬ 300 dpm/ng protein.…”

Adenovirus-mediated transfer of a gene encoding cholesterol 7 alpha-hydroxylase into hamsters increases hepatic enzyme activity and reduces plasma total and low density lipoprotein cholesterol.

“…Bile acid sequestrants such as cholestyramine bind bile acids in the intestinal lumen, thereby preventing their reabsorption. Loss of bile acids from the enterohepatic circulation results in derepression of 7a-hydroxylase expression (6)(7)(8)(9)(10) and an increase in the rate of bile acid synthesis (9,11). The liver compensates for the accelerated loss of cholesterol by increasing the rate of de novo cholesterol synthesis and, if this is inadequate, by increasing the receptordependent uptake of LDL from plasma (10), thereby lowering circulating LDL levels.…”