Sitosterol reduces messenger RNA and protein expression levels of Niemann-Pick C1-like 1 in FHs 74 Int cells

Elliot D. Jesch, Jeong Min Seo, Timothy P Carr, Ji Young Lee

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Intake of plant sterols has long been shown to reduce cholesterol absorption and subsequently plasma cholesterol concentrations. Despite competition between plant sterols and cholesterol for incorporation into mixed micelles as a suggested major mechanism for the inhibition of cholesterol absorption by plant sterols, studies exist to support an alternative mechanism. For example, another mechanism may be the action of plant sterols to reduce cholesterol absorption at the cellular level. This study was undertaken to test the hypothesis that plant sterols can modulate the expression of transporters such as Niemann-Pick C1-like 1 (NPC1L1) and scavenger receptor class B, type I (SR-BI) to lower intestinal cholesterol absorption. FHs 74 Int cells, a human small intestine epithelial cell line, were used as a model of enterocytes. The cells were treated with 25α-hydroxycholesterol (25 μmol/L) or 250 μmol/L of sitosterol, stigmasterol, and cholesterol for 24 hours to measure genes involved in cholesterol absorption and metabolism by quantitative real-time polymerase chain reaction. 25α-Hydroxycholesterol, cholesterol, and sitosterol significantly reduced the messenger RNA (mRNA) expression of NPC1L1 and hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, whereas SR-BI mRNA was not altered by the sterols. Western blot analysis confirmed the reduction in NPC1L1 by sterols. Depletion of cellular cholesterol by mevinolin, a cholesterol synthesis inhibitor, increased NPC1L1 and HMG-CoA reductase mRNA; and repletion of cholesterol abolished the increase. Sitosterol, but not stigmasterol, reduced the mRNA levels of NPC1L1 and HMG-CoA reductase to a similar extent of cholesterol. In conclusion, sitosterol can inhibit the expression of NPC1L1 in the enterocytes, which could be an alternate mechanism for plant sterols to reduce intestinal cholesterol uptake.

Original languageEnglish (US)
Pages (from-to)859-866
Number of pages8
JournalNutrition Research
Volume29
Issue number12
DOIs
StatePublished - Dec 1 2009

Fingerprint

Cholesterol
Messenger RNA
Phytosterols
Proteins
Coenzyme A
CD36 Antigens
Stigmasterol
Oxidoreductases
Enterocytes
Sterols
gamma-sitosterol
Anticholesteremic Agents
Lovastatin
Intestinal Absorption
Micelles
Small Intestine
Real-Time Polymerase Chain Reaction
Western Blotting
Epithelial Cells
Cell Line

Keywords

  • FHs 74 Int cells
  • NPC1L1
  • Plant sterol
  • SR-BI
  • cholesterol absorption
  • sitosterol
  • stigmasterol

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

Cite this

Sitosterol reduces messenger RNA and protein expression levels of Niemann-Pick C1-like 1 in FHs 74 Int cells. / Jesch, Elliot D.; Seo, Jeong Min; Carr, Timothy P; Lee, Ji Young.

In: Nutrition Research, Vol. 29, No. 12, 01.12.2009, p. 859-866.

Research output: Contribution to journalArticle

Jesch, Elliot D. ; Seo, Jeong Min ; Carr, Timothy P ; Lee, Ji Young. / Sitosterol reduces messenger RNA and protein expression levels of Niemann-Pick C1-like 1 in FHs 74 Int cells. In: Nutrition Research. 2009 ; Vol. 29, No. 12. pp. 859-866.
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