5 years ago

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

Phytosterol-mediated inhibition of intestinal cholesterol absorption in mice is independent of liver X receptor
Lídia Cedó, Petri T. Kovanen, José M. Carbó, Leena Kaipiainen, Joan Carles Escolà-Gil, Francisco Blanco-Vaca, Helena Gylling, Reija Silvennoinen, David Santos, Iziar A. Ludwig, Maria-José Motilva, Annabel F. Valledor, Annabel García-León, Miriam Lee-Rueckert
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. Phytosterols (PHY) and liver X receptors (LXR) induce similar effects on cholesterol homeostasis in the intestine. LXR activation reduces intestinal cholesterol absorption, and promotes transintestinal cholesterol excretion (TICE) and biliary cholesterol secretion. The present study confirms the crucial role of LXR in regulating whole-body cholesterol homeostasis, but demonstrates that the cholesterol-lowering effects of PHY are regulated in an LXR-independent manner.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/mnfr.201700055

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