ArticleJournal of lipid research2019
FTY720/fingolimod decreases hepatic steatosis and expression of fatty acid synthase in diet-induced nonalcoholic fatty liver disease in mice.
Article in Journal of lipid research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- Sphingolipid homeostasis and dysregulation in liver function and disease.Life metabolism · 2026Review
- Intestinal fungi shape the biology of the mammalian gut.PLoS pathogens · 2026Article
- F13A1-Mediated Macrophage Activation Promotes MASH Progression via the PKM2/HIF1A Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Opaganib Protects Against High-Fat Diet-Induced Hypercholesterolemia and Liver Steatosis in Mice.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Blocking Sphingosine 1-phosphate Metabolism With Fingolimod Prevents the Progression of Vascular Smooth Muscle Cells Calcification in Chronic Kidney Disease.Journal of cellular physiology · 2026Article
- Genomics-informed drug-repurposing strategy identifies two therapeutic targets for preventing liver disease associated with metabolic dysfunction.American journal of human genetics · 2025Article
- ECM remodeling in hypothyroidism-associated MAFLD: mechanisms, clinical relevance, and therapeutic targets.Frontiers in immunology · 2025Review
- Sphingosine kinase 2 (SphK2) depletion alters redox metabolism and enhances inflammation in a diet-induced MASH mouse model.Hepatology communications · 2024Article
- Fat-to-blood recirculation of partially dysfunctional PD-1iScience · 2024Article
- Therapeutic implications for sphingolipid metabolism in metabolic dysfunction-associated steatohepatitis.Frontiers in endocrinology · 2024Review
- Integrative roles of sphingosine kinase in liver pathophysiology.Toxicological research · 2023Review
- Histone Modifications in NAFLD: Mechanisms and Potential Therapy.International journal of molecular sciences · 2023Review
- Uncoupling Lipid Synthesis from Adipocyte Development.Biomedicines · 2023Article
- Adipose-specific deletion of the cation channel TRPM7 inhibits TAK1 kinase-dependent inflammation and obesity in male mice.Nature communications · 2023Article
- Article
- FTY720 Reduces Lipid Accumulation by Upregulating ABCA1 through Liver X Receptor and Sphingosine Kinase 2 Signaling in Macrophages.International journal of molecular sciences · 2022Article
- Molecular Advances in MAFLD-A Link between Sphingolipids and Extracellular Matrix in Development and Progression to Fibrosis.International journal of molecular sciences · 2022Review
- A new preclinical model of western diet-induced progression of non-alcoholic steatohepatitis to hepatocellular carcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Lipid alterations in chronic liver disease and liver cancer.JHEP reports : innovation in hepatology · 2022Review
- SIRT6 regulates SREBP1c-induced glucolipid metabolism in liver and pancreas via the AMPKα-mTORC1 pathway.Laboratory investigation; a journal of technical methods and pathology · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD), a leading cause of liver dysfunction, is a metabolic disease that begins with steatosis. Sphingolipid metabolites, particularly ceramide and sphingosine-1-phosphate (S1P), have recently received attention for their potential roles in insulin resistance and hepatic steatosis. FTY720/fingolimod, a prodrug for the treatment of multiple sclerosis, is phosphorylated in vivo to its active phosphorylated form by sphingosine kinase 2 and has been shown to interfere with the actions of S1P and to inhibit ceramide biosynthesis. Therefore, in this study we investigated the effects of FTY720 in a diet-induced animal model of NAFLD (DIAMOND) that recapitulates the hallmarks of the human disease. The oral administration of FTY720 to these mice fed a high-fat diet and sugar water improved glucose tolerance and reduced steatosis. In addition to decreasing liver triglycerides, FTY720 also reduced hepatic sphingolipid levels, including ceramides, monohexosylceramides, and sphingomyelins, particularly the C16:0 and C24:1 species, as well as S1P and dihydro-S1P. FTY720 administration decreased diet-induced fatty acid synthase (FASN) expression in DIAMOND mice without affecting other key enzymes in lipogenesis. FTY720 had no effect on the expression of SREBP-1c, which transcriptionally activates FASN. However, in agreement with the notion that the active phosphorylated form of FTY720 is an inhibitor of histone deacetylases, FTY720-P accumulated in the liver, and histone H3K9 acetylation was markedly increased in these mice. Hence, FTY720 might be useful for attenuating FASN expression and triglyceride accumulation associated with steatosis.
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