ArticleToxicology in vitro : an international journal published in association with BIBRA2017
Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system.
Article in Toxicology in vitro : an international journal published in association with BIBRA, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 33 citations in OpenAlex.
- Human cardiovascular disease model predicts xanthine oxidase inhibitor cardiovascular risk.PloS one · 2023Trial
- Obeticholic Acid and Other Farnesoid-X-Receptor (FXR) Agonists in the Treatment of Liver Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Effects of Obeticholic Acid Treatment on Primary Human Hepatocytes in a Novel Tri-Culture Model System.Cells · 2025Article
- Long Noncoding RNA TRIBAL Links the 8q24.13 Locus to Hepatic Lipid Metabolism and Coronary Artery Disease.Circulation. Genomic and precision medicine · 2024Article
- The roles of nuclear receptors in cholesterol metabolism and reverse cholesterol transport in nonalcoholic fatty liver disease.Hepatology communications · 2024Review
- Review
- Review
- A novel small molecule approach for the treatment of propionic and methylmalonic acidemias.Molecular genetics and metabolism · 2021Article
- Validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response.Scientific reports · 2021Article
- Farnesoid X receptor (FXR): Structures and ligands.Computational and structural biotechnology journal · 2021Review
- Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.Cell metabolism · 2019Article
- A nonalcoholic fatty liver disease model in human induced pluripotent stem cell-derived hepatocytes, created by endoplasmic reticulum stress-induced steatosis.Disease models & mechanisms · 2018Article
- Translating scientific discovery: the need for preclinical models of nonalcoholic steatohepatitis.Hepatology international · 2018Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Nonalcoholic steatohepatitis (NASH) is an emerging health crisis with no approved therapies. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, shows promise in NASH trials. However, the precise mechanisms mediating OCA effects and impact on cholesterol metabolism are not fully understood. We explored the pharmaco-toxicological effects of OCA on patho-physiological pathways in hepatocytes using a previously described perfused organotypic liver system that allows culture in near-physiological insulin/glucose milieus, and exhibits drug responses at clinically-relevant concentrations. Primary hepatocytes experienced 48-hour exposure to OCA at concentrations approximating therapeutic (0.5μM) and supratherapeutic (10μM) levels. Global transcriptomics by RNAseq was complimented by cellular viability (MTT), CYP activity assays, and secreted FGF19 levels in the media. Dose-dependent, transcriptional effects suggested suppression of bile acid synthesis (↓CYP7A1, ↓CYP27A1) and increased bile efflux (↑ABCB4, ↑ABCB11, ↑OSTA, ↑OSTB). Pleiotropic effects included suppression of TGFβ and IL-6 signaling pathways, and signatures suggestive of HDL suppression (↑SCARB1, ↓ApoAI, ↓LCAT) and LDL elevation (↑ApoB, ↓CYP7A1). OCA exhibited direct FXR-mediated effects with increased FGF19 secretion. Transcriptomics revealed regulation of metabolic, anti-inflammatory, and anti-fibrotic pathways beneficial in NASH, and predicted cholesterol profiles consistent with clinical findings. Follow-up studies under lipotoxic/inflammatory conditions would corroborate these effects in a disease-relevant environment.
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What OpenQuestion holds
Registered trials
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.