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Updated: Feb 10, 2026
Novel In Vivo Micro-Computed Tomography Imaging Techniques for Assessing the Progression of Non-Alcoholic Fatty Liver Disease
Published on: March 24, 2023
Novel therapeutic drug identification and gene correlation for fatty liver disease using high-content screening:
Wei-Jia Luo1, Ting-Yu Cheng1, Keng-Ieng Wong1
1Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Abstract:
Non-alcoholic fatty liver disease (NAFLD) is a problem in obese people caused by increasing intake of high-calorie food such as fructose implicated in the elevated prevalence. It is necessary to identify novel drugs to develop effective therapies. In this study, we combined LOPAC® (The Library of Pharmacologically Active Compounds) and High-Content screening to identify compounds that significantly reduced intracellular lipid droplets (LD) after high fat medium (HFM) treatment. Among 1280 compounds, we identified 239 compounds that reduced LD by >50%. Of these, 17 maintained cell viability. Nine of them were selected for validation using normal primary hepatocytes, of which five compounds showed dose-dependent efficacy. Whole genome transcriptomic network analysis was performed to construct the underlying regulatory network. There were 831 (711 up-regulated and 120 down-regulated genes) and 3480 (2009 up-regulated and 1471 down-regulated genes) genes that showed a significant change (>2-fold; p < 0.05) after 12 and 24 h HFM treatment, respectively. Gene enrichment and pathway analysis showed several immune responses mediated by MIF, IL-17, TLR, and IL-6. These compounds modulate lipogenesis via GSK3β and CREB1, which is followed by an alteration in the expression of several downstream genes related to hepatocellular carcinoma and hepatitis. CREB1 is a core transcription factor and may be a potential therapeutic target for liver disease. In conclusion, this proof of concept provides a strategy for identifying novel drugs for treatment of fatty liver disease as well as elucidates their underlying mechanisms. This research provides opportunity for developing future pharmaceutical therapeutics.
Insights
Researchers screened 1280 compounds to find new drugs for non-alcoholic fatty liver disease (NAFLD). Five compounds effectively reduced liver fat and showed potential therapeutic mechanisms, offering hope for future fatty liver disease treatments.
Area of Science:
- Hepatology and Pharmacology
- Drug Discovery and Development
- Genomics and Bioinformatics
Background:
- Non-alcoholic fatty liver disease (NAFLD) prevalence is rising, particularly in obese individuals, due to high-calorie diets.
- Effective therapeutic strategies for NAFLD are urgently needed.
- Identifying novel drug candidates is crucial for developing new treatments.
Purpose of the Study:
- To identify novel compounds that reduce lipid accumulation in liver cells.
- To elucidate the molecular mechanisms underlying the efficacy of identified compounds.
- To explore potential therapeutic targets for fatty liver disease.
Main Methods:
- High-content screening of the LOPAC® library (1280 compounds) against high-fat medium (HFM)-treated cells.
- Validation of hit compounds using primary hepatocytes and dose-response studies.
- Whole genome transcriptomic analysis to identify regulatory networks and pathways.
Main Results:
- 239 compounds reduced lipid droplets by over 50%, with 5 showing dose-dependent efficacy in primary hepatocytes.
- Transcriptomic analysis revealed significant gene expression changes after HFM treatment, impacting immune responses (MIF, IL-17, TLR, IL-6).
- Identified compounds modulate lipogenesis via GSK3β and CREB1, affecting genes related to hepatocellular carcinoma and hepatitis.
Conclusions:
- This study presents a successful strategy for discovering novel drugs for fatty liver disease.
- The identified compounds target key pathways like lipogenesis and inflammation, with CREB1 as a potential therapeutic target.
- The findings support the development of new pharmaceutical therapeutics for NAFLD and related liver conditions.
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