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Selective sterol accumulation in ABCG5/ABCG8-deficient mice
Liqing Yu1, Klaus von Bergmann, Dieter Lutjohann
1McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Journal of Lipid Research
|December 6, 2003
Summary
ATP binding cassette (ABC) transporters ABCG5 and ABCG8 prevent sitosterolemia by limiting sterol absorption and promoting biliary secretion. These transporters are crucial for preventing the accumulation of non-cholesterol sterols in the body.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- ATP binding cassette (ABC) transporters ABCG5 and ABCG8 regulate neutral sterol absorption and secretion.
- Mutations in ABCG5 or ABCG8 cause sitosterolemia, a disease characterized by elevated plasma and tissue sterol levels.
Purpose of the Study:
- To investigate the preferential accumulation of non-cholesterol sterols in sitosterolemia.
- To compare sterol levels in various tissues of wild-type and ABCG5/ABCG8-deficient mice.
Main Methods:
- Sterol levels (cholesterol and plant sterols) were measured in plasma, liver, bile, and brain of wild-type and ABCG5/ABCG8-deficient mice.
- mRNA levels of cholesterol biosynthetic enzymes were analyzed in mouse livers.
Main Results:
- ABCG5/ABCG8-deficient mice showed a 30-fold increase in non-cholesterol sterols but similar total sterol content compared to wild-type.
- Sterol enrichment in knockout mice mirrored their enrichment in wild-type mouse bile, indicating preferential biliary secretion.
- Reduced mRNA levels of cholesterol biosynthetic enzymes were observed in knockout mice despite lower hepatic cholesterol.
Conclusions:
- Preferential biliary secretion of specific non-cholesterol sterols by ABCG5 and ABCG8 prevents their accumulation in normal individuals.
- The accumulation of non-cholesterol sterols is recognized by the body's cholesterol regulatory system.