Attenuation of the Hepatoprotective Effects of Ileal Apical Sodium Dependent Bile Acid Transporter (ASBT) Inhibition in Choline-Deficient L-Amino Acid-Defined (CDAA) Diet-Fed Mice

Frontiers in Medicine
Anuradha RaoPaul A Dawson

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a major growing worldwide health problem. We previously reported that interruption of the enterohepatic circulation of bile acids using a non-absorbable apical sodium-dependent bile acid transporter inhibitor (ASBTi; SC-435) reduced the development of NAFLD in high fat diet fed mice. However, the ability of ASBTi treatment to impact the progression of NAFLD to non-alcoholic steatohepatitis (NASH) and fibrosis in a diet-induced mouse model remains untested. In the current study, we assessed whether ASBTi treatment is hepatoprotective in the choline-deficient, L-amino acid-defined (CDAA) diet model of NASH-induced fibrosis. Methods: Male C57Bl/6 mice were fed with: (A) choline-sufficient L-amino acid-defined diet (CSAA) (31 kcal% fat), (B) CSAA diet plus ASBTi (SC-435; 60 ppm), (C) CDAA diet, or (D) CDAA diet plus ASBTi. Body weight and food intake were monitored. After 22 weeks on diet, liver histology, cholesterol and triglyceride levels, and gene expression were measured. Fecal bile acid and fat excretion were measured, and intestinal fat absorption was determined using the sucrose polybehenate method. Results: ASBTi treatment reduced bodyweight gain in mice fed either the CSAA or C...Continue Reading

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Citations

Sep 18, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ivo P van de PeppelJohan W Jonker
Oct 21, 2020·Molecular Nutrition & Food Research·Ivo P van de PeppelJohan W Jonker
Oct 10, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Na YangYu-Bo Li
May 10, 2021·Cellular and Molecular Gastroenterology and Hepatology·David J MatyeTiangang Li

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Methods Mentioned

BETA
PCR

Software Mentioned

GraphPad
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