Phytosterol-mediated inhibition of intestinal cholesterol absorption in mice is independent of liver X receptor

Lídia Cedó, David Santos, Iziar A. Ludwig, Reija Silvennoinen, Annabel García-León, Leena Kaipiainen, José M. Carbó, Annabel F. Valledor, Helena Gylling, Maria José Motilva, Petri T. Kovanen, Miriam Lee-Rueckert, Francisco Blanco-Vaca, Joan Carles Escolà-Gil

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9 Citations (Scopus)

Abstract

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Scope: Previous studies have proposed that phytosterols activate liver X receptors (LXR) in the intestine, thereby reducing intestinal cholesterol absorption and promoting fecal cholesterol excretion. Methods and results: In the present study, we examined the effects of dietary phytosterol supplementation on intestinal cholesterol absorption and fecal neutral sterol excretion in LXRαβ-deficient mice, and wild-type mice treated with synthetic high-affinity LXRαβ agonists. LXRαβ deficiency led to an induction of intestinal cholesterol absorption and liver cholesterol accumulation. Phytosterol feeding resulted in an approximately 40% reduction of intestinal cholesterol absorption both in wild-type and LXRαβ-deficient mice, reduced dietary cholesterol accumulation in liver and promoted the excretion of fecal cholesterol-derived compounds. Furthermore, phytosterols produced additive inhibitory effects on cholesterol absorption in mice treated with LXRαβ agonists. Conclusions: Our data confirm the effect of LXR in regulating intestinal cholesterol absorption and demonstrate that the cholesterol-lowering effects of phytosterols occur in an LXR-independent manner.
Original languageEnglish
Article number1700055
JournalMolecular Nutrition and Food Research
Volume61
Issue number9
DOIs
Publication statusPublished - 1 Sep 2017

Keywords

  • Cholesterol
  • Intestine
  • Liver X receptor
  • Mice
  • Phytosterols

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    Cedó, L., Santos, D., Ludwig, I. A., Silvennoinen, R., García-León, A., Kaipiainen, L., Carbó, J. M., Valledor, A. F., Gylling, H., Motilva, M. J., Kovanen, P. T., Lee-Rueckert, M., Blanco-Vaca, F., & Escolà-Gil, J. C. (2017). Phytosterol-mediated inhibition of intestinal cholesterol absorption in mice is independent of liver X receptor. Molecular Nutrition and Food Research, 61(9), [1700055]. https://doi.org/10.1002/mnfr.201700055