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Phytosterol‐mediated inhibition of intestinal cholesterol absorption in mice is independent of liver X receptor
Author(s) -
Cedó Lídia,
Santos David,
Ludwig Iziar A.,
Silvennoinen Reija,
GarcíaLeón Annabel,
Kaipiainen Leena,
Carbó José M.,
Valledor Annabel F.,
Gylling Helena,
Motilva MariaJosé,
Kovanen Petri T.,
LeeRueckert Miriam,
BlancoVaca Francisco,
EscolàGil Joan Carles
Publication year - 2017
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201700055
Subject(s) - liver x receptor , phytosterol , cholesterol , medicine , endocrinology , sterol , excretion , chemistry , absorption (acoustics) , reverse cholesterol transport , abca1 , cholesterol 7 alpha hydroxylase , biology , biochemistry , nuclear receptor , transporter , lipoprotein , physics , transcription factor , acoustics , gene
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.