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Seven Steps to Stellate Cells
Published on: May 10, 2011
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Indole-3-propionic acid promotes hepatic stellate cells inactivation.
Mariana Ilha1,2, Ratika Sehgal1,3, Johanna Matilainen4
1Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Journal of Translational Medicine
|March 2, 2025
Summary
Lower levels of indole-3-propionic acid (IPA) are linked to liver fibrosis. This study shows IPA can induce apoptosis and inactivate hepatic stellate cells, suggesting a therapeutic role in suppressing liver fibrogenesis.
Area of Science:
- Hepatology
- Metabolomics
- Molecular Biology
Background:
- Serum levels of indole-3-propionic acid (IPA), a gut-derived tryptophan metabolite, are reduced in individuals with liver fibrosis.
- Previous research indicated a correlation between lower IPA levels and liver fibrosis.
Purpose of the Study:
- To investigate the transcriptome and DNA methylome associated with serum IPA levels in obese individuals.
- To explore the in vitro effects of IPA on shifting the hepatic stellate cell (HSC) phenotype towards inactivation.
Main Methods:
- Analysis of serum IPA, liver transcriptomics, and DNA methylation in 116 obese individuals.
- In vitro experiments using human hepatic stellate cells (LX-2) treated with IPA.
Main Results:
- Serum IPA levels correlated with liver gene expression in apoptosis, mitophagy, and longevity pathways.
- AKT serine/threonine kinase 1 (AKT1) emerged as a key interactive gene in both transcript and methylation profiles.
- IPA treatment in LX-2 cells induced apoptosis, reduced mitochondrial respiration, and modulated fibrosis-related gene expression.
Conclusions:
- IPA demonstrates potential therapeutic effects by inducing apoptosis and promoting HSC inactivation.
- Interfering with HSC activation and mitochondrial metabolism using IPA may offer a strategy to suppress hepatic fibrogenesis.
