Related Experiment Video
Updated: Jul 20, 2026

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
Hypercholesterolemia in rats with hepatomas: increased oxysterols accelerate efflux but do not inhibit biosynthesis
Takeshi Hirayama1, Akira Honda, Yasushi Matsuzaki
1Division of Gastroenterology and Hepatology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, and Kasumigaura Hospital, Ibaraki, Japan.
Abstract:
Hypercholesterolemia is an important paraneoplastic syndrome in patients with hepatoma, but the nature of this defect has not yet been identified. We investigated the molecular mechanisms of hypercholesterolemia in a hepatoma-bearing rat model. Buffalo rats were implanted in both flanks with Morris hepatoma 7777 (McA-RH7777) cells. After 4 weeks, tumor weight was 5.5+/-1.7 g, and serum cholesterol level increased from 60+/-2 to 90+/-2 mg/dL. Protein and mRNA expression of the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) was markedly higher in tumors than in livers. These increases were associated with activation of liver X receptor alpha (LXRalpha) as a result of the increased tissue oxysterol concentrations. The accumulation of oxysterols in the hepatomas appeared to be caused mainly by the upregulation of cholesterol biosynthesis, despite the increased tissue sterol concentrations. Overexpression of the sterol regulatory element-binding protein (SREBP) processing system relative to sterol concentration contributed to the resistance to sterols in this tumor. In addition, bile acid biosynthesis was inhibited despite the reduced expression of the small heterodimer partner (SHP) and activated LXRalpha, which also appeared to contribute to the accumulation of oxysterols followed by the acceleration of cholesterol efflux. In conclusion, hypercholesterolemia in McA-RH7777 hepatoma-bearing rats was caused by increased cholesterol efflux from tumors as a result of activation of LXRalpha. Overexpression of the SREBP processing system contributed to the activation of LXRalpha by maintaining high oxysterol levels in tissue.
Related Concept Videos
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Cholesterol: Significance and Regulation
Considering cholesterol and...
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Hepatic Drug Excretion: Influencing Factors
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
Hepatic Drug Clearance: Role of Transporters

