ArticleScientific reports2016
CHIP(-/-)-Mouse Liver: Adiponectin-AMPK-FOXO-Activation Overrides CYP2E1-Elicited JNK1-Activation, Delaying Onset of NASH: Therapeutic Implications.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
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- CHIP and aging: a key regulator of proteostasis and cellular senescence.Biogerontology · 2025Review
- The role of ubiquitination and deubiquitination in the pathogenesis of non-alcoholic fatty liver disease.Frontiers in immunology · 2025Review
- Role of AMPKZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- CHIP ameliorates nonalcoholic fatty liver disease via promoting K63- and K27-linked STX17 ubiquitination to facilitate autophagosome-lysosome fusion.Nature communications · 2024Article
- Uncovering the impact of alcohol on internal organs and reproductive health: Exploring TLR4/NF-kB and CYP2E1/ROS/Nrf2 pathways.Animal models and experimental medicine · 2024Review
- Transcriptomic analysis reveals pharmacological mechanisms mediating efficacy of Yangyinghuoxue Decoction in CCl4-induced hepatic fibrosis in rats.Frontiers in pharmacology · 2024Article
- Inter-organ metabolic interaction networks in non-alcoholic fatty liver disease.Frontiers in endocrinology · 2024Review
- Ubiquitination and Metabolic Disease.Advances in experimental medicine and biology · 2024Review
- CHIP Haploinsufficiency Exacerbates Hepatic Steatosis via Enhanced TXNIP Expression and Endoplasmic Reticulum Stress Responses.Antioxidants (Basel, Switzerland) · 2023Article
- Cardiovascular and lipid-lowering effects of a marine lipoprotein extract in a high-fat diet-induced obesity mouse model.International journal of medical sciences · 2023Article
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- STUB1-SMYD2 Axis Regulates Drug Resistance in Glioma cells.Journal of molecular neuroscience : MN · 2022Article
- CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload.International journal of molecular sciences · 2021Review
- ER Disposal Pathways in Chronic Liver Disease: Protective, Pathogenic, and Potential Therapeutic Targets.Frontiers in molecular biosciences · 2021Review
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- Multiple organs involved in the pathogenesis of non-alcoholic fatty liver disease.Cell & bioscience · 2020Review
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- Data on Adiponectin from 2010 to 2020: Therapeutic Target and Prognostic Factor for Liver Diseases?International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Genetic ablation of C-terminus of Hsc70-interacting protein (CHIP) E3 ubiquitin-ligase impairs hepatic cytochrome P450 CYP2E1 degradation. Consequent CYP2E1 gain of function accelerates reactive O2 species (ROS) production, triggering oxidative/proteotoxic stress associated with sustained activation of c-Jun NH2-terminal kinase (JNK)-signaling cascades, pro-inflammatory effectors/cytokines, insulin resistance, progressive hepatocellular ballooning and microvesicular steatosis. Despite this, little evidence of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) was found in CHIP(-/-)-mice over the first 8-9-months of life. We herein document that this lack of tissue injury is largely due to the concurrent up-regulation and/or activation of the adiponectin-5'-AMP-activated protein kinase (AMPK)-forkhead box O (FOXO)-signaling axis stemming from at the least three synergistic features: Up-regulated expression of adipose tissue adiponectin and its hepatic adipoR1/adipoR2 receptors, stabilization of hepatic AMPKα1-isoform, identified herein for the first time as a CHIP-ubiquitination substrate (unlike its AMPKα2-isoform), as well as nuclear stabilization of FOXOs, well-known CHIP-ubiquitination targets. Such beneficial predominance of the adiponectin-AMPK-FOXO-signaling axis over the sustained JNK-elevation and injurious insulin resistance in CHIP(-/-)-livers apparently counteracts/delays rapid progression of the hepatic microvesicular steatosis to the characteristic macrovesicular steatosis observed in clinical NASH and/or rodent NASH-models.
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Registered trials
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