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

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89 Scopus citations

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 7α-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 7α-hydroxylase activity and mRNA levels by 3-4-fold. Comparable effects on 7α-hydroxylase expression were observed with 1% cholestyramine. Psyllium also increased hepatic 7α-hydroxylase activity and mRNA in animals fed a diet enriched with cholesterol and triglyceride. Activation of 7α- 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 7α-hydroxylase and LDL metabolism that were similar to those of 1% cholestyramine. Induction of hepatic 7α- hydroxylase activity by dietary psyllium may account, in large part, for the hypocholesterolemic effect of this soluble fiber.

Original languageEnglish (US)
Pages (from-to)2084-2092
Number of pages9
JournalJournal of Clinical Investigation
Volume93
Issue number5
DOIs
StatePublished - May 1994

Keywords

  • 7α-hydroxylase
  • LDL transport
  • bile acids
  • cholesterol
  • dietary fiber
  • liver

ASJC Scopus subject areas

  • Medicine(all)

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