Stigmasterol stimulates transintestinal cholesterol excretion independent of liver X receptor activation in the small intestine

Hannah C. Lifsey, Rupinder Kaur, Bradley H. Thompson, Lisa Bennett, Ryan E. Temel, Gregory A. Graf

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Despite advances in healthcare, cardiovascular disease (CVD) remains the leading cause of death in the United States. Elevated levels of plasma cholesterol are highly predictive of CVD and stroke and are the principal driver of atherosclerosis. Unfortunately, current cholesterol lowering agents, such as statins, are not known to reverse atherosclerotic disease once it has been established. In preclinical models, agonists of nuclear receptor, LXR, have been shown to reduce and reverse atherosclerosis. Phytosterols are bioactive non-cholesterol sterols that act as LXR agonists and regulate cholesterol metabolism and transport. We hypothesized that stigmasterol would act as an LXR agonist and alter intestinal cholesterol secretion to promote cholesterol elimination. Mice were fed a control diet, or a diet supplemented with stigmasterol (0.3% w/w) or T0901317 (0.015% w/w), a known LXR agonist. In this experiment we analyzed the sterol content of bile, intestinal perfusate, plasma, and feces. Additionally, the liver and small intestine were analyzed for relative levels of transcripts known to be regulated by LXR. We observed that T0901317 robustly promoted cholesterol elimination and acted as a strong LXR agonist. Stigmasterol promoted transintestinal cholesterol secretion through an LXR-independent pathway.

Original languageEnglish
Article number108263
JournalJournal of Nutritional Biochemistry
Volume76
DOIs
StatePublished - Feb 2020

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • Bile
  • Cholesterol
  • LXR
  • Phytosterol
  • TICE

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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