ArticleArteriosclerosis, thrombosis, and vascular biology2013
Sphingomyelin synthase 2 activity and liver steatosis: an effect of ceramide-mediated peroxisome proliferator-activated receptor γ2 suppression.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 67 citations in OpenAlex.
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- Combining metabolomics and machine learning to discover biomarkers for early-stage breast cancer diagnosis.PloS one · 2024Article
- Q-RAI data-independent acquisition for lipidomic quantitative profiling.Scientific reports · 2023Article
- Substance P promotes epidural fibrosis via induction of type 2 macrophages.Neural regeneration research · 2023Article
- Effect of Total SMS Activity on LDL Catabolism in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Functional roles of sphingolipids in immunity and their implication in disease.Experimental & molecular medicine · 2023Review
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- De Novo Sphingolipid Biosynthesis in Atherosclerosis.Advances in experimental medicine and biology · 2022Article
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- Sphingomyelin Synthase Family and Phospholipase Cs.Advances in experimental medicine and biology · 2022Article
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- Sphingomyelin synthase 1 mediates hepatocyte pyroptosis to trigger non-alcoholic steatohepatitis.Gut · 2021Article
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- Effect of liver total sphingomyelin synthase deficiency on plasma lipid metabolism.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Article
- The role of Sphingomyelin synthase 2 (SMS2) in platelet activation and its clinical significance.Thrombosis journal · 2021Article
- Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveSphingolipid de novo biosynthesis is related to nonalcoholic fatty liver disease or hepatic steatosis. However, the mechanism is still unclear. Sphingomyelin synthase (SMS), using ceramide as one of the substrates to produce sphingomyelin, sits at the crossroads of sphingolipid biosynthesis. SMS has 2 isoforms: SMS1 and SMS2. SMS2 is the major isoform in liver. APPROACH AND
resultsTo investigate the relationship between liver SMS2 activity-mediated sphingolipid changes and hepatic steatosis, we used 2 mouse models: Sms2 liver-specific transgenic and Sms2 knockout mice. We found that Sms2 liver-specific transgenic livers have lower ceramide and higher sphingomyelin, whereas Sms2 knockout livers have higher ceramide and lower sphingomyelin. We also found that liver Sms2 overexpression promoted fatty acid uptake and liver steatosis, whereas Sms2 deficiency had an opposite effect in comparison with their respective controls. Importantly, the exogenous ceramide supplementation to Huh7 cells, a human hepatoma cell line, reduced the expression of peroxisome proliferator-activated receptor γ2 and its target genes, Cd36 and Fsp27. Peroxisome proliferator-activated receptor γ reporter analysis confirmed this phenomenon. Furthermore, peroxisome proliferator-activated receptor γ antagonist treatment significantly decreased triglyceride accumulation in Sms2 liver-specific transgenic liver.
conclusionsWe attributed these effects to ceramide that can suppress peroxisome proliferator-activated receptor γ2, thus reducing the expression of Cd36 and Fsp27 and reducing liver steatosis. After all, SMS2 inhibition in the liver could diminish liver steatosis.
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