ArticleExperimental & molecular medicine2019
Hepatic triglyceride accumulation via endoplasmic reticulum stress-induced SREBP-1 activation is regulated by ceramide synthases.
Article in Experimental & molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 474 citations in OpenAlex.
- A stress-adaptive lipid kinase axis defines metabolic vulnerabilities in neuroendocrine prostate cancer.Cancer cell · 2026Article
- Suppression of Post-Ischemic Cardiac Remodelling and Inflammatory Response by a Novel Sphingolipid Modifier, CIN038.International journal of molecular sciences · 2026Article
- A Stress-Adaptive Lipid Kinase Axis Defines Metabolic Vulnerabilities in Neuroendocrine Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- Targeted delivery of glucocerebrosidase to lysosomes: The LYSOTAC (LYSOsome-TArgeting Chimera) technology.Asian journal of pharmaceutical sciences · 2026Article
- Exploring Ceramide C16:0 as a Novel Biomarker and Therapeutic Target for Atherosclerosis.Journal of the American Heart Association · 2026Review
- Enavogliflozin, an SGLT2 Inhibitor, Improves Nonalcoholic Steatohepatitis Induced by High-Fat, High-Cholesterol Diet.Diabetes & metabolism journal · 2026Article
- Understanding Liver and Digestive Diseases: A Paved Road to Improve Diagnosis, Management, and Treatment.Exploration of digestive diseases · 2026Article
- Targeting Sphingolipids in Breast Cancer: From Tumor Biology to Therapeutic Strategies.Oncology research · 2026Review
- Reprogramming offspring liver health: maternal indole supplementation as a preventive strategy against MASLD.EBioMedicine · 2026Article
- Perilipin1 mediates milk fat synthesis in bovine mammary epithelial cells through SREBP1 phosphorylation.Animal biotechnology · 2025Article
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- Transcriptomics, lipidomics, and single-nucleus RNA sequencing integration: exploring sphingolipids in MASH-HCC progression.Cell & bioscience · 2025Article
- Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism.Cell research · 2025Article
- L-carnitine attenuates autophagic flux, apoptosis, and necroptosis in rats with dexamethasone-induced non-alcoholic steatohepatitis.BMC pharmacology & toxicology · 2024Article
- High-fat-diet-induced hepatic insulin resistanceiScience · 2024Article
- GR113808, a serotonin receptor 4 antagonist, prevents high-fat-diet-induced obesity, fatty liver formation, and insulin resistance in C57BL/6J mice.BMC pharmacology & toxicology · 2024Article
- Mechanism of Metabolic Dysfunction-associated Steatotic Liver Disease: Important role of lipid metabolism.Journal of clinical and translational hepatology · 2024Review
- The diverse roles of sphingolipids in inflammatory bowel disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Ceramides as Emerging Players in Cardiovascular Disease: Focus on Their Pathogenetic Effects and Regulation by Diet.Advances in nutrition (Bethesda, Md.) · 2024Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The endoplasmic reticulum (ER) is not only important for protein synthesis and folding but is also crucial for lipid synthesis and metabolism. In the current study, we demonstrate an important role of ceramide synthases (CerS) in ER stress and NAFLD progression. Ceramide is important in sphingolipid metabolism, and its acyl chain length is determined by a family of six CerS in mammals. CerS2 generates C22-C24 ceramides, and CerS5 or CerS6 produces C16 ceramide. To gain insight into the role of CerS in NAFLD, we used a high-fat diet (HFD)-induced NAFLD mouse model. Decreased levels of CerS2 and increased levels of CerS6 were observed in the steatotic livers of mice fed a HFD. In vitro experiments with Hep3B cells indicated the protective role of CerS2 and the detrimental role of CerS6 in the ER stress response induced by palmitate treatment. In particular, CerS6 overexpression increased sterol regulatory element-binding protein-1 (SREBP-1) cleavage with decreased levels of INSIG-1, leading to increased lipogenesis. Blocking ER stress abrogated the detrimental effects of CerS6 on palmitate-induced SREBP-1 cleavage. In accordance with the protective role of CerS2 in the palmitate-induced ER stress response, CerS2 knockdown enhanced ER stress and SREBP-1 cleavage, and CerS2 heterozygote livers exhibited a stronger ER stress response and higher triglyceride levels following HFD. Finally, treatment with a low dose of bortezomib increased hepatic CerS2 expression and protected the development of NAFLD following HFD. These results indicate that CerS and its derivatives impact hepatic ER stress and lipogenesis differently and might be therapeutic targets for NAFLD.
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