ArticleScience translational medicine2016
Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet-fed mice.
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 206 citations in OpenAlex.
- A randomised, double-blind, placebo-controlled phase 1 study of the safety, tolerability and pharmacodynamics of volixibat in overweight and obese but otherwise healthy adults: implications for treatment of non-alcoholic steatohepatitis.BMC pharmacology & toxicology · 2018Trial
- Safety, tolerability and pharmacodynamics of apical sodium-dependent bile acid transporter inhibition with volixibat in healthy adults and patients with type 2 diabetes mellitus: a randomised placebo-controlled trial.BMC gastroenterology · 2018Trial
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- Liver-specific SLC13A3 modulation alleviates MASLD by regulating NADMolecular and cellular biochemistry · 2026Article
- Cholestasis in Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- Article
- Taurochenodeoxycholic acid promotes abdominal fat deposition by modulating the crosstalk between bile acid metabolism and intestinal microbiota in broilers.Journal of animal science and biotechnology · 2025Article
- Critical Role of Cholic Acid in the Development of iHFC Diet-induced MASH in TSNO Mice.Inflammation · 2025Article
- Benefits and challenges to therapeutic targeting of bile acid circulation in cholestatic liver disease.Hepatology (Baltimore, Md.) · 2025Review
- Bile Acids and Type 2 Diabetes: Roles in Glucose Homeostasis and Therapeutic Opportunities.Metabolites · 2025Review
- Different types of bile acids exhibit opposite regulatory effects on lipid metabolism in finishing pigs through bile acid receptors.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- A Gallbladder-Specific Hydrophobic Bile Acid-FXR-MUC1 Signaling Axis Mediates Cholesterol Gallstone Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Role of Solute Carrier Family Transporters in Hepatic Steatosis and Hepatic Fibrosis.Journal of clinical and translational hepatology · 2025Review
- MetALD: Clinical aspects, pathophysiology and treatment.JHEP reports : innovation in hepatology · 2025Review
- Hepatic bile acid accretion correlates with cholestatic liver injury and therapeutic response inAmerican journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Chitosan-Stabilized Selenium Nanoparticles Alleviate High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease (NAFLD) by Modulating the Gut Barrier Function and Microbiota.Journal of functional biomaterials · 2024Article
- C9orf72 controls hepatic lipid metabolism by regulating SREBP1 transport.Cell death and differentiation · 2024Article
- The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications.Acta pharmaceutica Sinica. B · 2024Review
- Inhibition of hepatic bile salt uptake by Bulevirtide reduces atherosclerosis in Oatp1a1Journal of lipid research · 2024Article
- The GLP-1 Receptor Agonist Liraglutide Decreases Primary Bile Acids and Serotonin in the Colon Independently of Feeding in Mice.International journal of molecular sciences · 2024Article
62 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and safe and effective therapies are needed. Bile acids (BAs) and their receptors [including the nuclear receptor for BAs, farnesoid X receptor (FXR)] play integral roles in regulating whole-body metabolism and hepatic lipid homeostasis. We hypothesized that interruption of the enterohepatic BA circulation using a luminally restricted apical sodium-dependent BA transporter (ASBT) inhibitor (ASBTi; SC-435) would modify signaling in the gut-liver axis and reduce steatohepatitis in high-fat diet (HFD)-fed mice. Administration of this ASBTi increased fecal BA excretion and messenger RNA (mRNA) expression of BA synthesis genes in liver and reduced mRNA expression of ileal BA-responsive genes, including the negative feedback regulator of BA synthesis, fibroblast growth factor 15. ASBT inhibition resulted in a marked shift in hepatic BA composition, with a reduction in hydrophilic, FXR antagonistic species and an increase in FXR agonistic BAs. ASBT inhibition restored glucose tolerance, reduced hepatic triglyceride and total cholesterol concentrations, and improved NAFLD activity score in HFD-fed mice. These changes were associated with reduced hepatic expression of lipid synthesis genes (including liver X receptor target genes) and normalized expression of the central lipogenic transcription factor, Srebp1c Accumulation of hepatic lipids and SREBP1 protein were markedly reduced in HFD-fed Asbt(-/-) mice, providing genetic evidence for a protective role mediated by interruption of the enterohepatic BA circulation. Together, these studies suggest that blocking ASBT function with a luminally restricted inhibitor can improve both hepatic and whole body aspects of NAFLD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.