ArticleScientific reports2023
Combinatorial therapy with BAR502 and UDCA resets FXR and GPBAR1 signaling and reverses liver histopathology in a model of NASH.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Comparative effects of aerobic and resistance exercise on bile acid profiles and liver function in patients with non-alcoholic fatty liver disease.BMC gastroenterology · 2025Trial
- Gut‑liver‑kidney axis: A systems biology framework for understanding and treating chronic kidney disease (Review).International journal of molecular medicine · 2026Review
- Potential Therapeutic Strategies for Steatosis, Oxidative Stress, Inflammation, and Fibrosis in Liver Disease.International journal of molecular sciences · 2026Review
- Research Progress on the Mechanism and Targeted Intervention of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1)-Mediated "Inflammation-Apoptosis-Metabolism-Microcirculation" Regulatory Network in Hepatitis B-Associated Liver Failure.Drug design, development and therapy · 2026Review
- The role of bile acid-activated receptor TGR5 in inflammation and liver diseases.Frontiers in physiology · 2026Review
- Harnessing the Estradienone Scaffold to Develop Dual GPBAR1 and LIFR Modulators for Liver Fibrosis.Journal of medicinal chemistry · 2025Article
- 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
- Intermittent fasting and metabolic dysfunction-associated steatotic liver disease: the potential role of the gut-liver axis.Cell & bioscience · 2025Review
- Bile acids and their receptors in hepatic immunity.Liver research (Beijing, China) · 2025Review
- Review
- Pathophysiological Relationship between Type 2 Diabetes Mellitus and Metabolic Dysfunction-Associated Steatotic Liver Disease: Novel Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Bile acid and nonalcoholic steatohepatitis: Molecular insights and therapeutic targets.Journal of advanced research · 2024Review
- Quantitative Evaluation by Digital Pathology of Immunohistochemical Expression of CK7, CK19, and EpCAM in Advanced Stages of NASH.Biomedicines · 2024Article
- Farnesoid X Receptor Agonists: A Promising Therapeutic Strategy for Gastrointestinal Diseases.Gastro hep advances · 2024Review
- BAR502/fibrate conjugates: synthesis, biological evaluation and metabolic profile.Frontiers in chemistry · 2024Article
- Understanding the role of ursodeoxycholic acid and gut microbiome in non-alcoholic fatty liver disease: current evidence and perspectives.Frontiers in pharmacology · 2024Review
- The therapeutic mechanisms and beneficial effects of ursodeoxycholic acid in the treatment of nonalcoholic fatty liver disease: a systematic review.Medicine and pharmacy reports · 2024Review
- Current Therapeutical Approaches Targeting Lipid Metabolism in NAFLD.International journal of molecular sciences · 2023Review
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic steatosis (NAFLD) and steatohepatitis (NASH) are two highly prevalent human disorders for which therapy remains suboptimal. Bile acids are signaling molecules acting on two main receptors the Farnesoid-x-receptor (FXR) and G protein coupled receptor GPB AR1. Clinical trials have shown that FXR agonism might result in side effects along with lack of efficacy in restoring liver histopathology. For these reasons a multi-targets therapy combined FXR agonists with agent targeting additional molecular mechanisms might have improved efficacy over selective FXR agonists. In the present study we have compared the effects of BAR502, a dual FXR/GPBAR1 ligand) alone or in combination with ursodeoxycholic acid (UDCA) in a model of NAFLD/NASH induced by feeding mice with a Western diet for 10 weeks. The results demonstrated that while BAR502 and UDCA partially protected against liver damage caused by Western diet, the combination of the two, reversed the pro-atherogenic lipid profile and completely reversed the histopathology damage, attenuating liver steatosis, ballooning, inflammation and fibrosis. Additionally, while both agents increased insulin sensitivity and bile acid signaling, the combination of the two, modulated up top 85 genes in comparison of mice feed a Western diet, strongly reducing expression of inflammatory markers such as chemokines and cytokines. Additionally, the combination of the two agents redirected the bile acid metabolism toward bile acid species that are GPBAR1 agonist while reduced liver bile acid content and increased fecal excretion. Together, these data, highlight the potential role for a combinatorial therapy based on BAR502 and UDCA in treating of NAFLD.
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