ArticleNature communications2022
Induction of the hepatic aryl hydrocarbon receptor by alcohol dysregulates autophagy and phospholipid metabolism via PPP2R2D.
Article in Nature communications, 2022. 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, 34 citations in OpenAlex.
- Theabrownin Alleviates Alcoholic Liver Disease in Mice by Improving Gut Microbiota and Tryptophan Metabolism.Molecular nutrition & food research · 2026Article
- Indole-3-Propionic Acid Alleviates Metabolic Dysfunction-Associated Fatty Liver Disease via AHR/AMPK Signaling Activation.Food science & nutrition · 2026Article
- Expanded Tox21 Biological Assay Panel for the Prediction of Drug-Induced Liver Injury and Cardiotoxicity.Environmental health perspectives · 2026Article
- Aryl hydrocarbon receptor: a multifaceted environmental sensor in liver homeostasis and disease.Frontiers in medicine · 2026Review
- Neutrophil-T cell cross talk in noninfectious liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2026Review
- Compositional and Metabolomic Shifts of the Gut Microbiome in Alcohol-Related Liver Disease.Journal of gastroenterology and hepatology · 2025Review
- Type 2 Diabetes and the Multifaceted Gut-X Axes.Nutrients · 2025Review
- Glyoxalase 1 Inducer,Antioxidants (Basel, Switzerland) · 2025Article
- Ceramide kinase suppresses ferroptosis and protects against alcohol-associated liver disease through the p38 MAPK-HSPB1 pathway.Hepatology communications · 2025Article
- Binge drinking triggers VGLUT3-mediated glutamate secretion and subsequent hepatic inflammation by activating mGluR5/NOX2 in Kupffer cells.Nature communications · 2025Article
- Cinnabarinic acid protects against metabolic dysfunction-associated steatohepatitis by activating aryl hydrocarbon receptor-dependent AMPK signaling.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Metabolic Side Effects from Antipsychotic Treatment with Clozapine Linked to Aryl Hydrocarbon Receptor (AhR) Activation.Biomedicines · 2024Review
- Hepatic Gα13 ablation shifts region-specific colonic inflammatory status by modulating the bile acid synthetic pathway in mice.Scientific reports · 2024Article
- The IGF2BP3/Notch/Jag1 pathway: A key regulator of hepatic stellate cell ferroptosis in liver fibrosis.Clinical and translational medicine · 2024Article
- Article
- Multiomics Analysis of PCB126's Effect on a Mouse Chronic-Binge Alcohol Feeding Model.Environmental health perspectives · 2024Article
- MicroRNA-5010-5p ameliorates high-glucose induced inflammation in renal tubular epithelial cells by modulating the expression of PPP2R2D.BMJ open diabetes research & care · 2024Article
- Alcohol-related liver disease (ALD): current perspectives on pathogenesis, therapeutic strategies, and animal models.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Disturbed lipid metabolism precedes alcoholic liver injury. Whether and how AhR alters degradation of lipids, particularly phospho-/sphingo-lipids during alcohol exposure, was not explored. Here, we show that alcohol consumption in mice results in induction and activation of aryl hydrocarbon receptor (AhR) in the liver, and changes the hepatic phospho-/sphingo-lipids content. The levels of kynurenine, an endogenous AhR ligand, are elevated with increased hepatic tryptophan metabolic enzymes in alcohol-fed mice. Either alcohol or kynurenine treatment promotes AhR activation with autophagy dysregulation via AMPK. Protein Phosphatase 2 Regulatory Subunit-Bdelta (Ppp2r2d) is identified as a transcriptional target of AhR. Consequently, PPP2R2D-dependent AMPKα dephosphorylation causes autophagy inhibition and mitochondrial dysfunction. Hepatocyte-specific AhR ablation attenuates steatosis, which is associated with recovery of phospho-/sphingo-lipids content. Changes of AhR targets are corroborated using patient specimens. Overall, AhR induction by alcohol inhibits autophagy in hepatocytes through AMPKα, which is mediated by Ppp2r2d gene transactivation, revealing an AhR-dependent metabolism of phospho-/sphingo-lipids.
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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.