ArticleLiver international : official journal of the International Association for the Study of the Liver2014
Mixed lineage kinase 3 deficient mice are protected against the high fat high carbohydrate diet-induced steatohepatitis.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 53 citations in OpenAlex.
- Attack of the kinases: JNK signaling in metabolism.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Review
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- Knowledge mapping of exosomes in metabolic diseases: a bibliometric analysis (2007-2022).Frontiers in endocrinology · 2023Article
- MLK3 silence suppressed osteogenic differentiation and delayed bone formation via influencing the bone metabolism and disturbing MAPK signaling.Journal of orthopaedic translation · 2023Article
- Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease.Biomedicines · 2022Review
- Pathological Contribution of Extracellular Vesicles and Their MicroRNAs to Progression of Chronic Liver Disease.Biology · 2022Review
- Circulating cell-specific extracellular vesicles as biomarkers for the diagnosis and monitoring of chronic liver diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Extracellular Vesicles in Pathogenesis and Treatment of Metabolic Associated Fatty Liver Disease.Frontiers in physiology · 2022Review
- Stress kinases in the development of liver steatosis and hepatocellular carcinoma.Molecular metabolism · 2021Review
- Lipid-induced endothelial vascular cell adhesion molecule 1 promotes nonalcoholic steatohepatitis pathogenesis.The Journal of clinical investigation · 2021Article
- Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer.International journal of molecular sciences · 2021Review
- Protein Phosphatase 4 Promotes Hepatocyte Lipoapoptosis by Regulating RAC1/MLK3/JNK Pathway.Oxidative medicine and cellular longevity · 2021Article
- The role of stress kinases in metabolic disease.Nature reviews. Endocrinology · 2020Review
- Nonalcoholic Steatohepatitis Promoting Kinases.Seminars in liver disease · 2020Review
- Hepatic Deficiency of Augmenter of Liver Regeneration Predisposes to Nonalcoholic Steatohepatitis and Fibrosis.Hepatology (Baltimore, Md.) · 2020Observational
- Role of Extracellular Vesicles in the Pathophysiology, Diagnosis and Tracking of Non-Alcoholic Fatty Liver Disease.Journal of clinical medicine · 2020Review
- Liquid Biopsy for the Diagnosis of Viral Hepatitis, Fatty Liver Steatosis, and Alcoholic Liver Diseases.International journal of molecular sciences · 2020Review
- Current understanding of the role of Adipose-derived Extracellular Vesicles in Metabolic Homeostasis and Diseases: Communication from the distance between cells/tissues.Theranostics · 2020Review
- Article
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7 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsC-Jun N-terminal kinase (JNK) activation is pivotal in the development of nonalcoholic steatohepatitis (NASH). Mixed lineage kinase 3 (MLK) 3 is one of the mitogen activated protein kinase kinase kinase (MAP3K) that mediates JNK activation in the liver. Despite this concept, the role of MLK3 in modulating liver injury during nutrient excess has not been explored. Our aim was to determine if MLK3 deficient mice were protected against high fat high carbohydrate (HFHC) diet-induced NASH.
methodsWe employed eight-week-old Mlk3(-/-) male C57BL/6J mice, and wild type (WT) mice C57BL/6J as controls. Mice were fed a HFHC or a chow diet adlib for 16 weeks.
resultsHepatic JNK activating phosphorylation was readily absent in the Mlk3(-/-) mice fed the HFHC diet, but not in WT mice. This inhibition of JNK activation was hepatoprotective. Despite a comparable increase in weight gain, hepatic steatosis by histological examination and hepatic triglyceride quantification was reduced in HFHC diet-fed Mlk3(-/-) mice compared with WT mice. In addition, compared with the WT mice, HFHC diet-fed Mlk3(-/-) mice had significantly attenuated liver injury as manifested by reduced ALT levels, hepatocyte apoptosis, markers of hepatic inflammation and indices of hepatic fibrogenesis.
conclusionOur results suggest that loss of MLK3 in mice is protective against HFHC diet-induced NASH, in a weight-independent fashion, through attenuation of JNK activation. MLK3 is a potential therapeutic target for the treatment of human NASH.
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