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Related Experiment Videos

Gallstone formation in cholestanol-fed mice

K S Kim1, K Kano, N Hirabayashi

  • 1Department of Physiological Chemistry and Nutrition, Faculty of Medicine, University of Tokyo.

Journal of Biochemistry
|April 1, 1993
PubMed
Summary

Cholestanol (5 alpha-dihydrocholesterol) consumption leads to gallstones in mice by increasing cholesterol synthesis and decreasing bile acid production. Removing cholestanol reversed these metabolic effects.

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Area of Science:

  • Biochemistry
  • Metabolic Research
  • Gastroenterology

Background:

  • Cholesterol metabolism is crucial for physiological function.
  • Disruptions in bile acid and cholesterol balance can lead to gallstone formation.
  • The role of cholestanol in these processes requires further investigation.

Purpose of the Study:

  • To investigate the impact of dietary cholestanol on cholesterol and bile acid metabolism.
  • To determine the effects of cholestanol on gallstone development and gallbladder pathology.
  • To elucidate the mechanisms underlying cholestanol-induced metabolic changes.

Main Methods:

  • BALB/c mice were fed a diet containing 1% cholestanol for 14 months.
  • Serum and liver concentrations of cholestanol and cholesterol were measured.

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  • Hepatic microsomal enzyme activities (HMG-CoA reductase and cholesterol 7 alpha-hydroxylase) were assessed.
  • Gallstone composition and gallbladder histology were analyzed.

    • Main Results:

    • Mice fed cholestanol developed gallstones (55% cholesterol, 45% cholestanol) and gallbladder inflammation.
    • Serum and liver cholestanol levels significantly increased, while cholesterol levels decreased.
    • Hepatic HMG-CoA reductase activity (cholesterol synthesis) increased by 51%, and cholesterol 7 alpha-hydroxylase activity (bile acid synthesis) decreased by 59%.
    • Dietary withdrawal of cholestanol for one month normalized these metabolic parameters.

    Conclusions:

    • Cholestanol is absorbed and replaces cholesterol, leading to increased cholesterol synthesis and inhibited bile acid synthesis.
    • This metabolic imbalance promotes gallstone formation.
    • Cholestanol's effects on metabolism are reversible upon dietary withdrawal.