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

Hepatology. 2002 Oct;36(4 Pt 1):819-28. doi: 10.1053/jhep.2002.35617.


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 (-/-) mice. In conclusion, hepatic NPC1 expression is an important factor for regulating plasma HDL cholesterol levels and biliary cholesterol secretion in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Adenoviridae / genetics
  • Animal Feed
  • Animals
  • Bile Ducts, Extrahepatic / metabolism*
  • Cholesterol / blood
  • Cholesterol / metabolism
  • Cholesterol, Dietary / blood*
  • Gene Expression
  • Gene Transfer Techniques
  • Intracellular Signaling Peptides and Proteins
  • Lipoproteins / genetics
  • Liver / physiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Niemann-Pick Diseases / metabolism*
  • Proteins / genetics*


  • ATP-Binding Cassette Transporters
  • Cholesterol, Dietary
  • Intracellular Signaling Peptides and Proteins
  • Lipoproteins
  • Npc1 protein, mouse
  • Proteins
  • Cholesterol