ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Hepatic entrapment of esterified cholesterol drives continual expansion of whole body sterol pool in lysosomal acid lipase-deficient mice.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Targeting the lysosome: Mechanisms and treatments for nonalcoholic fatty liver disease.Journal of cellular biochemistry · 2022Review
- Article
- Defective Lysosomal Lipolysis Causes Prenatal Lipid Accumulation and Exacerbates Immediately after Birth.International journal of molecular sciences · 2021Article
- Persistent dyslipidemia in treatment of lysosomal acid lipase deficiency.Orphanet journal of rare diseases · 2020Article
- Ontogenesis and Modulation of Intestinal Unesterified Cholesterol Sequestration in a Mouse Model of Niemann-Pick C1 Disease.Digestive diseases and sciences · 2020Article
- Hepatocyte-specific deletion of lysosomal acid lipase leads to cholesteryl ester but not triglyceride or retinyl ester accumulation.The Journal of biological chemistry · 2019Article
- Genetically modified mouse models to study hepatic neutral lipid mobilization.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- Niemann-Pick C1-deficient mice lacking sterol O-acyltransferase 2 have less hepatic cholesterol entrapment and improved liver function.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- LAL (Lysosomal Acid Lipase) Promotes Reverse Cholesterol Transport In Vitro and In Vivo.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Impact of loss of SOAT2 function on disease progression in the lysosomal acid lipase-deficient mouse.Steroids · 2018Article
- Breaking fat: The regulation and mechanisms of lipophagy.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
- Quantitation of the rates of hepatic and intestinal cholesterol synthesis in lysosomal acid lipase-deficient mice before and during treatment with ezetimibe.Biochemical pharmacology · 2017Article
- Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover.The Journal of biological chemistry · 2016Article
- Article
- PRD125, a potent and selective inhibitor of sterol O-acyltransferase 2 markedly reduces hepatic cholesteryl ester accumulation and improves liver function in lysosomal acid lipase-deficient mice.The Journal of pharmacology and experimental therapeutics · 2015Article
- Deletion of sterol O-acyltransferase 2 (SOAT2) function in mice deficient in lysosomal acid lipase (LAL) dramatically reduces esterified cholesterol sequestration in the small intestine and liver.Biochemical and biophysical research communications · 2014Article
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7 authors at 1 institution in 1 country.
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Abstract
Cholesteryl ester storage disease (CESD) results from loss-of-function mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL). Hepatomegaly and deposition of esterified cholesterol (EC) in multiple organs ensue. The present studies quantitated rates of synthesis, absorption, and disposition of cholesterol, and whole body cholesterol pool size in a mouse model of CESD. In 50-day-old lal(-/-) and matching lal(+/+) mice fed a low-cholesterol diet, whole animal cholesterol content equalled 210 and 50 mg, respectively, indicating that since birth the lal(-/-) mice sequestered cholesterol at an average rate of 3.2 mg·day(-1)·animal(-1). The proportion of the body sterol pool contained in the liver of the lal(-/-) mice was 64 vs. 6.3% in their lal(+/+) controls. EC concentrations in the liver, spleen, small intestine, and lungs of the lal(-/-) mice were elevated 100-, 35-, 15-, and 6-fold, respectively. In the lal(-/-) 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(+/+) controls. The rate of cholesterol synthesis in the lal(-/-) mice exceeded that in the lal(+/+) controls by 3.7 mg·day(-1)·animal(-1). Fractional cholesterol absorption and fecal bile acid excretion were unchanged in the lal(-/-) mice, but their rate of neutral sterol excretion was 59% higher than in their lal(+/+) 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(-/-) mice was 355 days.
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