ArticleScience signaling2018
IRE1α prevents hepatic steatosis by processing and promoting the degradation of select microRNAs.
Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 114 citations in OpenAlex.
- The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturation.Nature communications · 2026Article
- The role of hepatocyte epigenetics in the pathogenesis of metabolic dysfunction-associated steatotic liver disease.Communications medicine · 2026Review
- Targeting endoplasmic reticulum stress: a novel therapeutic strategy for neuropathic pain.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- Microglial ER stress response via IRE1α regulates diet-induced metabolic imbalance and obesity in mice.Molecular metabolism · 2025Article
- Unfolded protein responses: Dynamic machinery in wound healing.Pharmacology & therapeutics · 2025Review
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
- Inhalation exposure to airborne PMAmerican journal of physiology. Cell physiology · 2025Article
- Lipophagy and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease progression in an experimental model.World journal of hepatology · 2024Article
- Discovery of a Compound That Inhibits IRE1αACS chemical biology · 2024Article
- Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models.Antioxidants (Basel, Switzerland) · 2024Article
- MOR23 deficiency exacerbates hepatic steatosis in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Obesity disrupts the pituitary-hepatic UPR communication leading to NAFLD progression.Cell metabolism · 2024Article
- Environmental PMeGastroenterology · 2024Article
- Two sides of the same coin: Non-alcoholic fatty liver disease and atherosclerosis.Vascular pharmacology · 2024Review
- Integrated traditional Chinese and Western medicine in the prevention and treatment of non-alcoholic fatty liver disease: future directions and strategies.Chinese medicine · 2024Review
- The Role of Endoplasmic Reticulum in Lipotoxicity during Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Pathogenesis.The American journal of pathology · 2023Review
- The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease-The Transition from an Adipocentric to Liver-Centric Approach.Current issues in molecular biology · 2023Review
- MicroRNA-34a Mediates High-Fat-Induced Hepatic Insulin Resistance by Targeting ENO3.Nutrients · 2023Article
- ATF4 suppresses hepatocarcinogenesis by inducing SLC7A11 (xCT) to block stress-related ferroptosis.Journal of hepatology · 2023Article
- The Unfolded Protein Response Sensor IRE1 Regulates Activation of In Vitro Differentiated Type 1 Conventional DCs with Viral Stimuli.International journal of molecular sciences · 2023Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 8 institutions in 2 countries.
Funding
Abstract
Obesity or a high-fat diet represses the endoribonuclease activity of inositol-requiring enzyme 1α (IRE1α), a transducer of the unfolded protein response (UPR) in cells under endoplasmic reticulum (ER) stress. An impaired UPR is associated with hepatic steatosis and nonalcoholic fatty liver disease (NAFLD), which is caused by lipid accumulation in the liver. We found that IRE1α was critical to maintaining lipid homeostasis in the liver by repressing the biogenesis of microRNAs (miRNAs) that regulate lipid mobilization. In mice fed normal chow, the endoribonuclease function of IRE1α processed a subset of precursor miRNAs in the liver, including those of the miR-200 and miR-34 families, such that IRE1α promoted their degradation through the process of regulated IRE1-dependent decay (RIDD). A high-fat diet in mice or hepatic steatosis in patients was associated with the S-nitrosylation of IRE1α and inactivation of its endoribonuclease activity. This resulted in an increased abundance of these miRNA families in the liver and, consequently, a decreased abundance of their targets, which included peroxisome proliferator-activated receptor α (PPARα) and the deacetylase sirtuin 1 (SIRT1), regulators of fatty acid oxidation and triglyceride lipolysis. IRE1α deficiency exacerbated hepatic steatosis in mice. The abundance of the miR-200 and miR-34 families was also increased in cultured, lipid-overloaded hepatocytes and in the livers of patients with hepatic steatosis. Our findings reveal a mechanism by which IRE1α maintains lipid homeostasis through its regulation of miRNAs, a regulatory pathway distinct from the canonical IRE1α-UPR pathway under acute ER stress.
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Registered trials
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.