ArticleJCI insight2021
Differential role of MLKL in alcohol-associated and non-alcohol-associated fatty liver diseases in mice and humans.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Innate immune sensing of dietary alcohol ignites inflammation to drive alcohol-related disease.Science advances · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Targeting necroptosis: how does exercise protect against metabolic dysfunction-associated fatty liver disease?Frontiers in physiology · 2026Review
- An Update on Animal Models of Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- Linear ubiquitination prevents lipodystrophy and obesity-associated metabolic syndrome.Science advances · 2025Article
- Life-threatening risk factors contribute to the development of diseases with the highest mortality through the induction of regulated necrotic cell death.Cell death & disease · 2025Review
- Divergent roles of RIPK3 and MLKL in high-fat diet-induced obesity and MAFLD in mice.Life science alliance · 2025Article
- Immunology and treatments of fatty liver disease.Archives of toxicology · 2025Review
- Deletion of Mixed Lineage Kinase Domain Like Pseudokinase Aggravates Chronic Alcohol-Induced Liver Injury via Increasing Apoptosis.Digestive diseases and sciences · 2024Article
- Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions.World journal of gastroenterology · 2024Review
- Cell Death in Liver Disease and Liver Surgery.Biomedicines · 2024Review
- Non-Necroptotic Roles of MLKL in Diet-Induced Obesity, Liver Pathology, and Insulin Sensitivity: Insights from a High-Fat, High-Fructose, High-Cholesterol Diet Mouse Model.International journal of molecular sciences · 2024Article
- Mediators of necroptosis: from cell death to metabolic regulation.EMBO molecular medicine · 2024Review
- Distinct Types of Cell Death and Implications in Liver Diseases: An Overview of Mechanisms and Application.Journal of clinical and translational hepatology · 2023Review
- Absence of Either Ripk3 or Mlkl Reduces Incidence of Hepatocellular Carcinoma Independent of Liver Fibrosis.Molecular cancer research : MCR · 2023Article
- MLKL signaling regulates macrophage polarization in acute pancreatitis through CXCL10.Cell death & disease · 2023Article
- From (Tool)Bench to Bedside: The Potential of Necroptosis Inhibitors.Journal of medicinal chemistry · 2023Review
- Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease.Annual review of pathology · 2023Review
- CD47-SIRPα axis blockade in NASH promotes necroptotic hepatocyte clearance by liver macrophages and decreases hepatic fibrosis.Science translational medicine · 2022Article
- Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care.Gastroenterology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 8 institutions in 3 countries.
Funding
Abstract
Hepatocellular death contributes to progression of alcohol-associated (ALD-associated) and non-alcohol-associated (NAFL/NASH) liver diseases. However, receptor-interaction protein kinase 3 (RIP3), an intermediate in necroptotic cell death, contributes to injury in murine models of ALD but not NAFL/NASH. We show here that a differential role for mixed-lineage kinase domain-like protein (MLKL), the downstream effector of RIP3, in murine models of ALD versus NAFL/NASH and that RIP1-RIP3-MLKL can be used as biomarkers to distinguish alcohol-associated hepatitis (AH) from NASH. Phospho-MLKL was higher in livers of patients with NASH compared with AH or healthy controls (HCs). MLKL expression, phosphorylation, oligomerization, and translocation to plasma membrane were induced in WT mice fed diets high in fat, fructose, and cholesterol but not in response to Gao-binge (acute on chronic) ethanol exposure. Mlkl-/- mice were not protected from ethanol-induced hepatocellular injury, which was associated with increased expression of chemokines and neutrophil recruitment. Circulating concentrations of RIP1 and RIP3, but not MLKL, distinguished patients with AH from HCs or patients with NASH. Taken together, these data indicate that MLKL is differentially activated in ALD/AH compared with NAFL/NASH in both murine models and patients. Furthermore, plasma RIP1 and RIP3 may be promising biomarkers for distinguishing AH and NASH.
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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.