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Indole-3-Propionic Acid Alleviates Metabolic Dysfunction-Associated Fatty Liver Disease via AHR/AMPK Signaling
Yanting Huang1, Meimei Yu1, Jiaxin Lu1
1Department of Nutrition and Food Hygiene, School of Public Health Guangzhou Medical University Guangzhou China.
Food Science & Nutrition
|August 8, 2026
Summary
Indole-3-propionic acid (IPA) reduces liver fat accumulation in metabolic dysfunction-associated fatty liver disease (MAFLD). IPA activates the AHR/AMPK pathway, decreasing lipid synthesis and improving fatty liver in mice.
Area of Science:
- Hepatology
- Molecular Biology
- Biochemistry
Background:
- Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing global health concern characterized by excessive liver lipid accumulation.
- Indole-3-propionic acid (IPA) has shown potential in ameliorating MAFLD, but its precise mechanism in regulating hepatic lipid synthesis is not fully understood.
Purpose of the Study:
- To investigate the regulatory mechanism by which indole-3-propionic acid (IPA) affects hepatic lipid synthesis and alleviates MAFLD.
- To elucidate the role of the AHR/AMPK signaling pathway in IPA's therapeutic effects on MAFLD.
Main Methods:
- In vitro studies utilized FFA-induced HepG2 cells treated with IPA, assessing lipid accumulation via Oil Red O staining, and analyzing AHR/AMPK signaling through RNA-seq and Western blotting.
- Pharmacological inhibitors and agonists for AHR and AMPK were employed to explore IPA's regulatory mechanism.
- In vivo studies involved administering IPA to high-fat diet-fed C57BL/6J mice, followed by histopathological evaluation and pathway activation assessment.
Main Results:
- IPA demonstrated a dose-dependent reduction in lipid deposition in HepG2 cells.
- IPA inhibited lipid synthesis by activating the Aryl hydrocarbon Receptor (AHR) and promoting AMP-activated protein kinase (AMPK) phosphorylation, leading to downregulation of SREBP-1c and FAS.
- Pharmacological experiments confirmed that IPA-induced AMPK activation is AHR-dependent, and identified a bidirectional crosstalk between AHR and AMPK signaling.
Conclusions:
- Indole-3-propionic acid (IPA) alleviates MAFLD by reducing high-fat diet-induced hepatic lipid deposition.
- IPA exerts its protective effects through the activation of the AHR/AMPK signaling pathway, highlighting a potential therapeutic strategy for MAFLD.
