Impact of loss of SOAT2 function on disease progression in the lysosomal acid lipase-deficient mouse.
Steroids
; 130: 7-14, 2018 02.
Article
en En
| MEDLINE
| ID: mdl-29246491
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-â¯/- 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Esterol O-Aciltransferasa
/
Esterol Esterasa
Límite:
Animals
Idioma:
En
Revista:
Steroids
Año:
2018
Tipo del documento:
Article
Pais de publicación:
Estados Unidos