Relevance of Niemann-Pick type C1 protein expression in controlling plasma cholesterol and biliary lipid secretion in mice

Ludwig Amigo, Hegaly Mendoza, Juan Castro, Verónica Quiones, Juan Francisco Miquel, Silvana Zanlungo

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

59 Citas (Scopus)


Receptor-mediated endocytosis is one of the major mechanisms for uptake of lipoprotein cholesterol in the liver. Because Niemann-Pick C1 (NPC1) protein is a key component in the intracellular distribution of cholesterol obtained from lipoproteins by the endocytic pathway, it may play a critical role in controlling plasma lipoprotein cholesterol and its biliary secretion. A murine model of Niemann-Pick type C disease (NPC), the NPC1-deficient [NPC1 (-/-)] mouse, was used to evaluate the relevance of hepatic NPC1 expression in regulating plasma lipoprotein cholesterol profile and biliary lipid secretion under chow and high-cholesterol diets. Total plasma cholesterol concentrations were increased in NPC1 (-/-) mice compared with wild-type mice when both mouse strains were fed chow or high-cholesterol diets. The increased plasma cholesterol levels found in NPC1 (-/-) mice were mostly due to elevated cholesterol content in larger and more heterogeneous HDL particles. On the chow diet, biliary lipid secretion was not impaired by NPC1 deficiency. Furthermore, chow-fed NPC1 (-/-) mice showed a small, but significant, increase in biliary cholesterol secretion. On the high-cholesterol diet, wild-type mice increased biliary cholesterol output, whereas NPC1 (-/-) mice did not. Finally, hepatic NPC1 overexpression by adenovirus-mediated gene transfer increased biliary cholesterol secretion by 100% to 150% in both wild-type mice and cholesterol-fed NPC1 (-1-) mice. In conclusion, hepatic NPC1 expression is an important factor for regulating plasma HDL cholesterol levels and biliary cholesterol secretion in mice.

Idioma originalInglés
Páginas (desde-hasta)819-828
Número de páginas10
N.º4 I
EstadoPublicada - 1 oct. 2002

Áreas temáticas de ASJC Scopus

  • Hepatología


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