ArticleInternational journal of experimental pathology2014
Therapeutic reversal of chronic alcohol-related steatohepatitis with the ceramide inhibitor myriocin.
Article in International journal of experimental pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Review
- Tissue Microarray Lipidomic Imaging Mass Spectrometry Method: Application to the Study of Alcohol-Related White Matter Neurodegeneration.Applied biosciences · 2023Article
- Therapeutic Effects of Myriocin in Experimental Alcohol-Related Neurobehavioral Dysfunction and Frontal Lobe White Matter Biochemical Pathology.Journal of behavioral and brain science · 2022Article
- Myriocin Treatment Reverses Alcohol-Induced Alterations in Polyunsaturated Fatty Acid-Containing Phospholipid Expression in the Liver.Nutrition and metabolic insights · 2022Article
- Sphingolipids and the link between alcohol and cancer.Chemico-biological interactions · 2020Review
- Alcohol effects on hepatic lipid metabolism.Journal of lipid research · 2020Review
- The protective effect of quercetin in the alcohol-induced liver and lymphoid tissue injuries in newborns.Molecular biology reports · 2020Article
- Seipin negatively regulates sphingolipid production at the ER-LD contact site.The Journal of cell biology · 2019Article
- Enhanced Alcohol Preference and Anxiolytic Alcohol Effects in Niemann-Pick Disease Model in Mice.Frontiers in neurology · 2019Article
- Ethanol and C2 ceramide activate fatty acid oxidation in human hepatoma cells.Scientific reports · 2018Article
- The role of sphingolipids in psychoactive drug use and addiction.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- A novel role for ceramide synthase 6 in mouse and human alcoholic steatosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism.Scientific reports · 2017Article
- Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system.Cell death & disease · 2016Article
- Alcoholic, Nonalcoholic, and Toxicant-Associated Steatohepatitis: Mechanistic Similarities and Differences.Cellular and molecular gastroenterology and hepatology · 2015Review
- Endoplasmic reticulum heat shock protein gp96 maintains liver homeostasis and promotes hepatocellular carcinogenesis.Journal of hepatology · 2015Article
- [Role of ceramide in the pathogenesis of alcoholic fatty liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2015Article
- Chronic alcohol consumption potentiates the development of diabetes through pancreatic β-cell dysfunction.World journal of biological chemistry · 2015Review
- Sphingolipids and mitochondrial function, lessons learned from yeast.Microbial cell (Graz, Austria) · 2014Review
- New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases.International journal of hepatology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Alcohol-related liver disease (ALD) is associated with steatohepatitis and insulin resistance. Insulin resistance impairs growth and disrupts lipid metabolism in hepatocytes. Dysregulated lipid metabolism promotes ceramide accumulation and oxidative stress, leading to lipotoxic states that activate endoplasmic reticulum (ER) stress pathways and worsen inflammation and insulin resistance. In a rat model of chronic alcohol feeding, we characterized the effects of a ceramide inhibitor, myriocin, on the histopathological and ultrastructural features of steatohepatitis, and the biochemical and molecular indices of hepatic steatosis, insulin resistance and ER stress. Myriocin reduced the severity of alcohol-related steatohepatitis including the abundance and sizes of lipid droplets and mitochondria, inflammation and architectural disruption of the ER. In addition, myriocin-mediated reductions in hepatic lipid and ceramide levels were associated with constitutive enhancement of insulin signalling through the insulin receptor and IRS-2, reduced hepatic oxidative stress and modulation of ER stress signalling mechanisms. In conclusion, ceramide accumulation in liver mediates tissue injury, insulin resistance and lipotoxicity in ALD. Reducing hepatic ceramide levels can help restore the structural and functional integrity of the liver in chronic ALD due to amelioration of insulin resistance and ER stress. However, additional measures are needed to protect the liver from alcohol-induced necroinflammatory responses vis-à-vis continued alcohol abuse.
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Registered trials
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