ArticleJournal of gastroenterology and hepatology2013
Ceramide inhibitor myriocin restores insulin/insulin growth factor signaling for liver remodeling in experimental alcohol-related steatohepatitis.
Article in Journal of gastroenterology and hepatology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- The Acid sphingomyelinase/ceramide System in Idiopathic Inflammatory Myopathies: a Potential Treatment Target.Inflammation · 2026Review
- Review
- Molecular and biochemical pathologies in human alcohol-related cerebellar white matter degeneration.Advances in drug and alcohol research · 2025Article
- Dietary Soy Prevents Alcohol-Mediated Neurocognitive Dysfunction and Associated Impairments in Brain Insulin Pathway Signaling in an Adolescent Rat Model.Biomolecules · 2022Article
- Novel potential biomarkers for severe alcoholic liver disease.Frontiers in immunology · 2022Article
- Ceramide contributes to pathogenesis and may be targeted for therapy in VCP inclusion body myopathy.Human molecular genetics · 2021Article
- 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
- Direct and maternal n-3 long-chain polyunsaturated fatty acid supplementation improved triglyceridemia and glycemia through the regulation of hepatic and muscle sphingolipid synthesis in offspring hamsters fed a high-fat diet.European journal of nutrition · 2016Article
- Optimized Expression and Purification of Humbug in Pichia pastoris and Its Monoclonal Antibody Preparation.Iranian journal of public health · 2015Article
- Insulin resistance in clinical and experimental alcoholic liver disease.Annals of the New York Academy of Sciences · 2015Review
- [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
- Pharmacological ceramide reduction alleviates alcohol-induced steatosis and hepatomegaly in adiponectin knockout mice.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Absence of perilipin 2 prevents hepatic steatosis, glucose intolerance and ceramide accumulation in alcohol-fed mice.PloS one · 2014Article
- Phosphorylation Modulates Aspartyl-(Asparaginyl)-β Hydroxylase Protein Expression, Catalytic Activity and Migration in Human Immature Neuronal Cerebellar Cells.Cell biology : research & therapy · 2013Article
- The role of ceramides in the pathophysiology of diabetic retinopathy: Mechanisms and Implications for therapeutic strategies.Diabetes & vascular disease researchReview
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimAlcohol-related liver disease (ALD) is mediated in part by insulin resistance. Attendant dysregulation of lipid metabolism increases accumulation of hepatic ceramides that worsen insulin resistance and compromise the structural and functional integrity of the liver. Insulin and insulin growth factor (IGF) stimulate aspartyl-asparaginyl-β-hydroxylase (AAH), which promotes cell motility needed for structural maintenance and remodeling of the liver. AAH mediates its effects by activating Notch, and in ALD, insulin/IGF signaling, AAH, and Notch are inhibited.
methodTo test the hypothesis that in ALD, hepatic ceramide load contributes to impairments in insulin, AAH, and Notch signaling, control and chronic ethanol-fed adult Long-Evans rats were treated with myriocin, an inhibitor of serine palmitoyl transferase. Livers were used to assess steatohepatitis, insulin/IGF pathway activation, and expression of AAH-Notch signaling molecules.
resultsChronic ethanol-fed rats had steatohepatitis with increased ceramide levels; impairments in signaling through the insulin receptor, insulin receptor substrate, and Akt; and decreased expression of AAH, Notch, Jagged, Hairy-Enhancer of Split-1, hypoxia-inducible factor 1α, and proliferating cell nuclear antigen. Myriocin abrogated many of these adverse effects of ethanol, particularly hepatic ceramide accumulation, steatohepatitis, and impairments of insulin signaling through Akt, AAH, and Notch.
conclusionsIn ALD, the histopathology and impairments in insulin/IGF responsiveness can be substantially resolved by ceramide inhibitor treatments, even in the context of continued chronic ethanol exposure.
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