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Hepatic Niemann-Pick C1-like 1
Camilla Pramfalk1, Zhao-Yan Jiang, Paolo Parini
1Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Current Opinion in Lipidology
|April 16, 2011
Summary
Niemann-Pick C1-like 1 (NPC1L1) protein influences cholesterol metabolism in the liver, impacting biliary cholesterol and gallstone disease. Further human studies are needed to fully understand its hepatic functions.
Area of Science:
- Hepatology
- Cholesterol Metabolism
- Molecular Biology
Background:
- The discovery of Niemann-Pick C1-like 1 (NPC1L1) highlights the intestine's role in cholesterol homeostasis.
- Rodent models, unlike humans, do not express NPC1L1 in the liver, limiting understanding of its hepatic function.
Purpose of the Study:
- To review recent advancements in understanding the role of hepatic NPC1L1 in cholesterol metabolism.
- To explore NPC1L1's function in the liver, which remains incompletely defined.
Main Methods:
- Review of recent scientific literature on NPC1L1 and hepatic cholesterol metabolism.
- Analysis of studies involving human NPC1L1 expression in mice and gallstone patients.
Main Results:
- Mice expressing human NPC1L1 in the liver showed reduced biliary cholesterol, suggesting NPC1L1's role in biliary cholesterol reabsorption.
- Decreased hepatic NPC1L1 expression in women with gallstones suggests sex-based differences in cholesterol gallstone disease.
- Transcription factors like SREBP-2 and HNF-1α modulate NPC1L1 expression.
Conclusions:
- NPC1L1 is implicated in biliary cholesterol uptake, HDL metabolism, and cholesterol gallstone disease.
- Human studies are crucial for a comprehensive understanding of NPC1L1's liver functions.
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