ArticleJournal of hepatology2014
ASMase regulates autophagy and lysosomal membrane permeabilization and its inhibition prevents early stage non-alcoholic steatohepatitis.
Article in Journal of hepatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 106 citations in OpenAlex.
- Contradictory Effects on Hepatocytes in ASMD.International journal of molecular sciences · 2026Review
- The Acid sphingomyelinase/ceramide System in Idiopathic Inflammatory Myopathies: a Potential Treatment Target.Inflammation · 2026Review
- Coenzyme Q10 Supplementation Modulates Hepatic Lipidomic Alterations and Attenuates Metabolic Dysfunction-Associated Steatohepatitis in Mice.Nutrients · 2026Article
- Bibliometric Analysis of Emerging Trends and Hotspots in the Links between Nonalcoholic Steatohepatitis and Diabetes Mellitus from 2004 to 2023.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Comprehensive characterization of lysosome-dependent cell death reveals prognostic significance and immune landscape in colon adenocarcinoma.Scientific reports · 2025Article
- Acid sphingomyelinase promotes diabetic cardiomyopathy via disruption of mitochondrial calcium homeostasis.Cardiovascular diabetology · 2025Article
- TMEM175 activity in BK-deficient macrophages maintains lysosomal function and mediates silica-induced inflammatory response in macrophages.Inhalation toxicology · 2025Article
- Emerging roles of the acid sphingomyelinase/ceramide pathway in metabolic and cardiovascular diseases: Mechanistic insights and therapeutic implications.World journal of cardiology · 2025Review
- Puerarin Reversing Autophagy-Lysosomal Dysfunction via Acid Sphingomyelinase Inhibition in Cardiomyocytes.Journal of cellular and molecular medicine · 2025Article
- Mechanisms and therapeutic implications of selective autophagy in nonalcoholic fatty liver disease.Journal of advanced research · 2025Review
- Depressive symptom as a risk factor for cirrhosis in patients with primary biliary cholangitis: Analysis based on Lasso-logistic regression and decision tree models.Brain and behavior · 2024Article
- Article
- Autophagy and hepatic lipid metabolism: mechanistic insight and therapeutic potential for MASLD.npj metabolic health and disease · 2024Review
- Therapeutic implications for sphingolipid metabolism in metabolic dysfunction-associated steatohepatitis.Frontiers in endocrinology · 2024Review
- The relevance of acid sphingomyelinase as a potential target for therapeutic intervention in hepatic disorders: current scenario and anticipated trends.Archives of toxicology · 2023Review
- Modulation of Dietary Choline Uptake in a Mouse Model of Acid Sphingomyelinase Deficiency.International journal of molecular sciences · 2023Article
- Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation.European journal of cell biology · 2023Article
- Functional roles of sphingolipids in immunity and their implication in disease.Experimental & molecular medicine · 2023Review
- Association between antidepressant use and liver fibrosis in patients with type 2 diabetes: a population based study.Diabetology & metabolic syndrome · 2023Article
- High Fat Diet Mediated Alterations in Serum Sphingolipid Profiles in An Experimental Mouse Model Measured by Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry.European journal of biology and biotechnology · 2023Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 12 institutions in 6 countries.
Funding
Abstract
BACKGROUND &
aimsAcid sphingomyelinase (ASMase) is activated in non-alcoholic steatohepatitis (NASH). However, the contribution of ASMase to NASH is poorly understood and limited to hepatic steatosis and glucose metabolism. Here we examined the role of ASMase in high fat diet (HFD)-induced NASH.
methodsAutophagy, endoplasmic reticulum (ER) stress and lysosomal membrane permeabilization (LMP) were determined in ASMase(-/-) mice fed a HFD. The impact of pharmacological ASMase inhibition on NASH was analyzed in wild type mice fed a HFD.
resultsASMase deficiency determined resistance to hepatic steatosis mediated by a HFD or methionine-choline deficient diet. ASMase(-/-) mice were resistant to HFD-induced hepatic ER stress, but sensitive to tunicamycin-mediated ER stress, indicating selectivity in the resistance of ASMase(-/-) mice to ER stress and steatosis. Autophagic flux, determined in the presence of rapamycin and/or chloroquine, was lower in primary mouse hepatocytes (PMH) from ASMase(-/-) mice and accompanied by increased p62 levels, suggesting autophagic impairment. Moreover, autophagy suppression by chloroquine and brefeldin A caused ER stress in PMH from ASMase(+/+) mice but not in ASMase(-/-) mice. ASMase(-/-) PMH exhibited increased lysosomal cholesterol loading, decreased LMP and apoptosis resistance induced by O-methyl-serine dodecylamide hydrochloride or palmitic acid, effects that were reversed by decreasing cholesterol levels by oxysterol 25-hydroxycholesterol. In vivo pharmacological ASMase inhibition by amitriptyline, a widely used tricyclic antidepressant, protected wild type mice against HFD-induced hepatic steatosis, fibrosis, and liver damage, effects indicative of early-stage NASH.
conclusionsThese findings underscore a critical role for ASMase in diet-induced NASH and suggest the potential of amitriptyline as a treatment for patients with NASH.
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