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In 50-day-old lal<jats:sup>\u2212\/\u2212<\/jats:sup>and matching lal<jats:sup>+\/+<\/jats:sup>mice fed a low-cholesterol diet, whole animal cholesterol content equalled 210 and 50 mg, respectively, indicating that since birth the lal<jats:sup>\u2212\/\u2212<\/jats:sup>mice sequestered cholesterol at an average rate of 3.2 mg\u00b7day<jats:sup>\u22121<\/jats:sup>\u00b7animal<jats:sup>\u22121<\/jats:sup>. The proportion of the body sterol pool contained in the liver of the lal<jats:sup>\u2212\/\u2212<\/jats:sup>mice was 64 vs. 6.3% in their lal<jats:sup>+\/+<\/jats:sup>controls. EC concentrations in the liver, spleen, small intestine, and lungs of the lal<jats:sup>\u2212\/\u2212<\/jats:sup>mice were elevated 100-, 35-, 15-, and 6-fold, respectively. In the lal<jats:sup>\u2212\/\u2212<\/jats:sup>mice, whole liver cholesterol synthesis increased 10.2-fold, resulting in a 3.2-fold greater rate of whole animal sterol synthesis compared with their lal<jats:sup>+\/+<\/jats:sup>controls. The rate of cholesterol synthesis in the lal<jats:sup>\u2212\/\u2212<\/jats:sup>mice exceeded that in the lal<jats:sup>+\/+<\/jats:sup>controls by 3.7 mg\u00b7day<jats:sup>\u22121<\/jats:sup>\u00b7animal<jats:sup>\u22121<\/jats:sup>. Fractional cholesterol absorption and fecal bile acid excretion were unchanged in the lal<jats:sup>\u2212\/\u2212<\/jats:sup>mice, but their rate of neutral sterol excretion was 59% higher than in their lal<jats:sup>+\/+<\/jats:sup>controls. Thus, in this model, the continual expansion of the body sterol pool is driven by the synthesis of excess cholesterol, primarily in the liver. Despite the severity of their disease, the median life span of the lal<jats:sup>\u2212\/\u2212<\/jats:sup>mice was 355 days.<\/jats:p>","DOI":"10.1152\/ajpgi.00243.2014","type":"journal-article","created":{"date-parts":[[2014,8,22]],"date-time":"2014-08-22T07:56:42Z","timestamp":1408694202000},"page":"G836-G847","source":"Crossref","is-referenced-by-count":25,"title":["Hepatic entrapment of esterified cholesterol drives continual expansion of whole body sterol pool in lysosomal acid lipase-deficient mice"],"prefix":"10.1152","volume":"307","author":[{"given":"Amal","family":"Aqul","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam M.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, 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