Critical role of cholic acid for development of hypercholesterolemia and gallstones in diabetic mice

Biochem Biophys Res Commun. 2006 Apr 21;342(4):1382-8. doi: 10.1016/j.bbrc.2006.02.108. Epub 2006 Feb 28.

Abstract

We studied bile acid and cholesterol metabolism in insulin-dependent diabetes utilizing genetically modified mice unable to synthesize cholic acid (Cyp8b1-/-). Diabetes was induced in Cyp8b1-/- and wild type animals (Cyp8b1+/+) by alloxan, and the mice were fed normal or cholesterol-enriched diet for 10 weeks. The serum levels of cholesterol were strongly increased in diabetic Cyp8b1+/+ mice fed cholesterol, while diabetic Cyp8b1-/- mice did not show any aberrations regardless of the diet. Diabetic cholesterol-fed Cyp8b1+/+ mice had much higher biliary cholesterol and cholesterol saturation index than all other groups, their bile contained a large number of cholesterol crystals, and their canalicular cholesterol transporter Abcg5/g8 mRNA levels were much higher. Cyp7a1 mRNA levels were similar in all diabetic mice but higher compared to non-diabetic animals. The results indicate a critical role for cholic acid for the development of hypercholesterolemia and gallstones in our animal model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alloxan
  • Animals
  • Cholesterol, Dietary / metabolism*
  • Cholic Acid / deficiency
  • Cholic Acid / metabolism*
  • Diabetes Complications / chemically induced
  • Diabetes Complications / metabolism*
  • Disease Models, Animal*
  • Gallstones / etiology
  • Gallstones / metabolism*
  • Hypercholesterolemia / etiology
  • Hypercholesterolemia / metabolism*
  • Male
  • Mice

Substances

  • Cholesterol, Dietary
  • Alloxan
  • Cholic Acid