Diosgenin stimulation of fecal cholesterol excretion in mice is not NPC1L1 dependent

Ryan E. Temel, J. Mark Brown, Yinyan Ma, Weiqing Tang, Lawrence L. Rudel, Yiannis A. Ioannou, Joanna P. Davies, Liqing Yu

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Diosgenin exists in some food supplements and herbal medicines and lowers plasma cholesterol by increasing fecal cholesterol excretion. It is believed that diosgenin promotes fecal cholesterol excretion by stimulating biliary cholesterol secretion and decreasing intestinal cholesterol absorption. Niemann-Pick C1-like 1 (NPC1L1) was recently identified as an essential protein for intestinal cholesterol absorption. To determine the relative contribution of biliary secretion and intestinal absorption of cholesterol in diosgenin-stimulated fecal cholesterol excretion, wild-type (WT) and NPC1L1-knockout (L1KO) mice were fed a diet with or without 1% diosgenin. Fecal cholesterol excretion (μmol/day/100 g body weight) increased in diosgenin-fed WT and L1KO mice from 4.2 to 52 and from 63 to 140, respectively. Surprisingly, this increase in diosgenin-treated versus untreated L1KO mice (77) was even greater than that seen in diosgenin-treated versus untreated WT mice (47.8). Additionally, WT and L1KO mice fed the diosgenin diet had similar increases in biliary cholesterol concentration, despite unaltered hepatic expression of the hepatobiliary cholesterol transporter, ATP binding cassette transporters G5 and G8. Facilitated cholesterol excretion in diosgenin-treated WT and L1KO mice was associated with decreased hepatic and plasma cholesterol and increased liver expression of cholesterol synthetic genes. In contrast, diosgenin had no effect on the intestinal expression of NPC1L1 and cholesterol synthetic genes. In an in vitro assay, diosgenin was unable to block NPC1L1-dependent cholesterol uptake. In conclusion, diosgenin stimulation of fecal cholesterol excretion is independent of NPC1L1-mediated cholesterol absorption.

Original languageEnglish
Pages (from-to)915-923
Number of pages9
JournalJournal of Lipid Research
Volume50
Issue number5
DOIs
StatePublished - May 2009

Keywords

  • Bile
  • Feces
  • Intestine

Fingerprint

Dive into the research topics of 'Diosgenin stimulation of fecal cholesterol excretion in mice is not NPC1L1 dependent'. Together they form a unique fingerprint.

Cite this