ArticleMolecular metabolism2019
The pseudokinase MLKL regulates hepatic insulin sensitivity independently of inflammation.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 109 citations in OpenAlex.
- Adipocyte caspase-8 but not RIPK3 promotes adiposity.Cell death discovery · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- MLKL in liver parenchymal cells promotes liver cancer in murine metabolic dysfunction-associated steatotic liver disease.Cell death & disease · 2026Article
- Shifting cell death modes in hepatic steatosis: from apoptosis to necroptosis.Endocrine journal · 2026Review
- Targeting necroptosis: how does exercise protect against metabolic dysfunction-associated fatty liver disease?Frontiers in physiology · 2026Review
- DNA2 acts as a brake on β cell insulin hypersecretion and diet-induced metabolic dysfunction.Frontiers in cell and developmental biology · 2026Article
- TNF as a mediator of metabolic inflammation and body-brain interaction in obesity-driven neuroinflammation and neurodegeneration.Ageing research reviews · 2025Review
- Adipocyte-specific Mlkl knockout mitigates obesity-induced metabolic dysfunction by enhancing mitochondrial functions.Cell death & disease · 2025Article
- Linear ubiquitination prevents lipodystrophy and obesity-associated metabolic syndrome.Science advances · 2025Article
- Mixed Lineage Kinase Domain-Like Protein (MLKL): From Mechanisms to Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Impact of Mlkl or Ripk3 deletion on age-associated liver inflammation, metabolic health, and lifespan.GeroScience · 2025Article
- Pathological Glucose Levels Enhance Entry Factor Expression and Hepatic SARS-CoV-2 Infection.Journal of cellular and molecular medicine · 2025Article
- Mixed lineage kinase domain-like protein in liver diseases: Cell-type-specific functions and dual roles.World journal of gastroenterology · 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
- Agomelatine Mitigates Kidney Damage in Obese Insulin-Resistant Rats by Inhibiting Inflammation and Necroptosis via the TNF-α/NF-ĸB/p-RIPK3 Pathway.International journal of molecular sciences · 2025Article
- A determination of the main regulators of necroptosis in testicular tissue under different heat stresses.Journal of molecular histology · 2025Article
- Divergent roles of RIPK3 and MLKL in high-fat diet-induced obesity and MAFLD in mice.Life science alliance · 2025Article
- MLKL promotes hepatocarcinogenesis through inhibition of AMPK-mediated autophagy.Cell death and differentiation · 2024Article
- 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
- Sestrin2 maintains hepatic immune homeostasis and redox balance partially via inhibiting RIPK3-mediated necroptosis in metabolic dysfunction-associated steatohepatitis.Molecular metabolism · 2024Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe mixed lineage kinase domain like (MLKL) protein, receptor interacting protein (RIPK) 1, and RIPK3 are key regulators of necroptosis, a highly pro-inflammatory mode of cell death that has been implicated in various pathological processes and human diseases. However, the role of these necroptotic regulators in diabetes remains unknown. Here we sought to delineate the role of MLKL in insulin resistance and type 2 diabetes (T2D).
methodsWe first analyzed the expression of key necroptotic regulators in obese/diabetic mouse models. We then utilized MLKL knockout (MLKL
resultsIn wild-type or obese mice (ob/ob, db/db, or diet-induced obesity), MLKL was increased in certain obesity-associated tissues, particularly in the liver. Whole-body deficiency of MLKL prevented obesity-induced insulin resistance and glucose intolerance. Inhibition of MLKL or other key necroptotic regulators enhanced hepatic insulin sensitivity. MLKL modulated insulin-stimulated PI(3,4,5)P3 production in liver cells but did not affect the expression of inflammatory genes in vitro and in vivo. Nec-1 administration ameliorated insulin resistance and glucose intolerance in ob/ob mice.
conclusionsThese findings reveal MLKL as a regulator of insulin sensitivity and suggest necroptotic regulators might be potential therapeutic targets for insulin resistance and T2D.
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