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

Biochemical and Biophysical Research Communications
Jin WangGösta Eggertsen

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.

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Citations

Aug 6, 2016·Journal of Clinical and Experimental Hepatology·Lisa-Mari MörkEwa C S Ellis
Oct 24, 2014·Diabetes·Achint KaurMichael R Hayden
Jul 29, 2006·Pharmacology & Therapeutics·Irina A Pikuleva
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Nov 19, 2019·International Journal of Endocrinology·Mengsiyu LiShuguang Pang
Apr 6, 2017·American Journal of Physiology. Endocrinology and Metabolism·Enrico BertaggiaRebecca A Haeusler
Sep 21, 2018·Current Diabetes Reports·Karolina E Zaborska, Bethany P Cummings

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