Inborn Errors of Metabolism that Lead to Permanent Liver Injury

Ghishan, Fayez K.

doi:10.1016/b978-1-4160-3258-8.50074-7

Cited by 2 publications

(1 citation statement)

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“…Tissue EC levels are elevated in a number of rare diseases [3] including Tangier disease [15], Wolman disease (WD) and Cholesteryl Ester Storage Disease (CESD) [16, 17]. These latter disorders result from mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL) [18].…”

Section: Introductionmentioning

confidence: 99%

Impact of loss of SOAT2 function on disease progression in the lysosomal acid lipase-deficient mouse

Lopez

Chuang

Turley³

2018

Steroids

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Although only a small proportion of cholesterol in the body is esterified, in several diseases marked expansion of the esterified cholesterol (EC) pool occurs. These include Wolman disease (WD) and Cholesteryl Ester Storage Disease (CESD) which both result from mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL). The respective contributions that our three cholesterol esterifying enzymes make to EC production, especially in disorders like CESD, are not well defined. The current studies represent a detailed exploration of our earlier findings in young male LAL-deficient mice also missing sterol O-acyltransferase 2 (SOAT2, also called ACAT2). Here we show that, even as they aged, male and female Lal: Soat2 mice, compared to Lal: Soat2 littermates, had appreciably less hepatomegaly as well as a marked reduction in the level of sequestration of EC, in liver transaminase activities, and in hepatic mRNA expression levels for markers of inflammation. Loss of SOAT2 function also dramatically curtailed EC entrapment in the small intestine of the LAL-deficient mice. Together, these data imply that SOAT2 inhibition, if applied concurrently with enzyme replacement therapy for LAL deficiency, may blunt the re-esterification of newly released unesterified cholesterol thereby improving clinical outcomes.

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Section: Introductionmentioning

confidence: 99%