Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice

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

[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.This work was partly funded by the Ministerio de Sanidady Consumo, Instituto de Salud Carlos III, and FEDER “Unamanera de hacer Europa,” grants FIS 14–01648 (to F.B.-V.) andFIS 16–00139 (to J.C.E.-G.), grant FJCI-2014-20689 from theMinisterio de Econom ́ıa, Industria y Competitividad (to I.A.L.)and grant 12/C/2015 from La Fundaci ́o la Marato TV3 (to F.B-V). CIBER de Diabetes y Enfermedades Metab ́olicas Asociadas isan Instituto de Salud Carlos III Project.Peer reviewe