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

Adam M. Lopez, Jen Chieh Chuang, Stephen D. Turley

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7-14
Number of pages8
JournalSteroids
Volume130
DOIs
StatePublished - Feb 1 2018

Fingerprint

Sterol Esterase
Disease Progression
Cholesterol
Cholesterol Ester Storage Disease
Cholesterol Esters
Wolman Disease
Sterol O-Acyltransferase
Enzyme Replacement Therapy
Hepatomegaly
Esterification
Liver
Transaminases
Small Intestine
mouse lysosomal acid lipase
Genes
Inflammation
Messenger RNA
Mutation
Enzymes

Keywords

  • Cholesteryl ester storage disease
  • Hepatomegaly
  • Liver transaminase activity
  • Small intestine
  • Triacylglycerol

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Impact of loss of SOAT2 function on disease progression in the lysosomal acid lipase-deficient mouse. / Lopez, Adam M.; Chuang, Jen Chieh; Turley, Stephen D.

In: Steroids, Vol. 130, 01.02.2018, p. 7-14.

Research output: Contribution to journalArticle

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