Hepatic cholesterol homeostasis: is the low-density lipoprotein pathway a regulatory or a shunt pathway?
Arterioscler Thromb Vasc Biol
; 33(11): 2481-90, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23990208
ABSTRACT
OBJECTIVE:
The hypothesis that cholesterol that enters the cell within low-density lipoprotein (LDL) particles rapidly equilibrates with the regulatory pool of intracellular cholesterol and maintains cholesterol homeostasis by reducing cholesterol and LDL receptor synthesis was validated in the fibroblast but not in the hepatocyte. Accordingly, the present studies were designed to compare the effects of cholesterol that enters the hepatocyte within an LDL particle with those of cholesterol that enters via other lipoprotein particles. APPROACH ANDRESULTS:
We measured cholesterol synthesis and esterification in hamster hepatocytes treated with LDL and other lipoprotein particles, including chylomicron remnants and VLDL. Endogenous cholesterol synthesis was not significantly reduced by uptake of LDL, but cholesterol esterification (280%) and acyl CoAcholesterol acyltransferase 2 expression (870%) were increased. In contrast, cholesterol synthesis was significantly reduced (70% decrease) with other lipoprotein particles. Furthermore, more cholesterol that entered the hepatocyte within LDL particles was secreted within VLDL particles (480%) compared with cholesterol from other sources.CONCLUSIONS:
Much of the cholesterol that enters the hepatocyte within LDL particles is shunted through the cell and resecreted within VLDL particles without reaching equilibrium with the regulatory pool.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
VLDL-Colesterol
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Hepatócitos
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Metabolismo dos Lipídeos
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Homeostase
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LDL-Colesterol
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article