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

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.

• Authors: Jin Wang, Mats Gåfvels, Mats Rudling, Charlotte Murphy, Ingemar Björkhem, Curt Einarsson, Gösta Eggertsen
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 342 Issue 4 Pg. 1382-8 (Apr 21 2006) ISSN: 0006-291X [Print] United States
• PMID: 16516849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol, Dietary
• Alloxan
• Cholic Acid

Topics

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