Liver X receptor agonist modulation of cholesterol efflux in mice with intestine-specific deletion of microsomal triglyceride transfer protein.

Arteriosclerosis, Thrombosis, and Vascular Biology
Yan XieNicholas O Davidson

Abstract

Previous work demonstrated that intestinal cholesterol absorption and regulated expression of intestinal Niemann-Pick C1-like 1 and ATP-binding cassette protein A1 are required for liver X receptor (LXR) agonist-mediated increases in high-density lipoprotein biogenesis. We re-examined those conclusions in mice with intestine-specific deletion of the microsomal triglyceride transfer protein (MTTP-IKO), where chylomicron formation is eliminated. MTTP-IKO mice demonstrated sustained ≈90% reduction in cholesterol absorption and >80% reduction in Niemann-Pick C1-like 1 expression, yet LXR agonist treatment increased serum high-density lipoprotein and upregulated intestinal ATP-binding cassette protein A1 expression. Hepatic lipogenesis and triglyceride content increased with LXR agonist treatment in both genotypes. Biliary cholesterol secretion was increased in MTTP-IKO mice without further increase upon LXR agonist administration. LXR agonist treatment caused a paradoxical increase in cholesterol absorption in MTTP-IKO mice and decreased fecal neutral sterol excretion, but to levels that still exceeded fecal neutral sterol excretion in LXR agonist-treated control mice. Finally, MTTP-IKO mice demonstrated indistinguishable patterns ...Continue Reading

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Citations

Jul 30, 2014·Journal of Lipid Research·Chiara DegirolamoAntonio Moschetta
Apr 21, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yan XieNicholas O Davidson
Jul 26, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Amy M GarciaDeborah C Rubin
Nov 14, 2017·Journal of the American Animal Hospital Association·Mandy L WallaceEric Monnet

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