ArticleJournal of lipid research2015
SphK1 mediates hepatic inflammation in a mouse model of NASH induced by high saturated fat feeding and initiates proinflammatory signaling in hepatocytes.
Article in Journal of lipid research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 90 citations in OpenAlex.
- Sphingolipid homeostasis and dysregulation in liver function and disease.Life metabolism · 2026Review
- Higher Plasma Sphingosine-1-Phosphate Levels in Type 2 Diabetic Patients Have a Non-Linear Relationship with the Disease Prognostic Indices and Microvascular Complications: A Cross-Sectional Saudi Study.Journal of clinical medicine · 2026Article
- F13A1-Mediated Macrophage Activation Promotes MASH Progression via the PKM2/HIF1A Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hypoxia-inducible factor 2α overexpression in podocytes ameliorates lipid metabolism disorders in diabetic kidney disease by inhibiting S1P.Renal failure · 2025Article
- Regulatory role of S1P and its receptors in sepsis-induced liver injury.Frontiers in immunology · 2025Review
- Adipocyte sphingosine kinase 1 regulates histone modifiers to disrupt circadian function.bioRxiv : the preprint server for biology · 2024Article
- Sphingosine kinase 1 is induced by glucocorticoids in adipose derived stem cells and enhances glucocorticoid mediated signaling in adipose expansion.bioRxiv : the preprint server for biology · 2024Article
- Influence of SphK1 on Inflammatory Responses in Lipopolysaccharide-Challenged RAW 264.7 Cells.Cell biochemistry and biophysics · 2024Article
- SGLT2 inhibition leads to a restoration of hepatic and circulating metabolites involved in the folate cycle and pyrimidine biosynthesis.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Therapeutic implications for sphingolipid metabolism in metabolic dysfunction-associated steatohepatitis.Frontiers in endocrinology · 2024Review
- Effect of FTY720P on lipid accumulation in HEPG2 cells.Scientific reports · 2023Article
- Integrative roles of sphingosine kinase in liver pathophysiology.Toxicological research · 2023Review
- Comprehensive Strategy for Identifying Extracellular Vesicle Surface Proteins as Biomarkers for Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2023Review
- Novel oral SPT inhibitor CH5169356 inhibits hepatic stellate cell activation and ameliorates hepatic fibrosis in mouse models of non-alcoholic steatohepatitis (NASH).Pharmacology research & perspectives · 2023Article
- ORMDL in metabolic health and disease.Pharmacology & therapeutics · 2023Review
- Identification of a Specific Plasma Sphingolipid Profile in a Group of Normal-Weight and Obese Subjects: A Novel Approach for a "Biochemical" Diagnosis of Metabolic Syndrome?International journal of molecular sciences · 2023Article
- Neutrophil CEACAM1 determines susceptibility to NETosis by regulating the S1PR2/S1PR3 axis in liver transplantation.The Journal of clinical investigation · 2023Article
- Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development.Immunity · 2023Article
- The Crosstalk between FcεRI and Sphingosine Signaling in Allergic Inflammation.International journal of molecular sciences · 2022Review
- Molecular Advances in MAFLD-A Link between Sphingolipids and Extracellular Matrix in Development and Progression to Fibrosis.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Steatohepatitis occurs in up to 20% of patients with fatty liver disease and leads to its primary disease outcomes, including fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma. Mechanisms that mediate this inflammation are of major interest. We previously showed that overload of saturated fatty acids, such as that which occurs with metabolic syndrome, induced sphingosine kinase 1 (SphK1), an enzyme that generates sphingosine-1-phosphate (S1P). While data suggest beneficial roles for S1P in some contexts, we hypothesized that it may promote hepatic inflammation in the context of obesity. Consistent with this, we observed 2-fold elevation of this enzyme in livers from humans with nonalcoholic fatty liver disease and also in mice with high saturated fat feeding, which recapitulated the human disease. Mice exhibited activation of NFκB, elevated cytokine production, and immune cell infiltration. Importantly, SphK1-null mice were protected from these outcomes. Studies in cultured cells demonstrated saturated fatty acid induction of SphK1 message, protein, and activity, and also a requirement of the enzyme for NFκB signaling and increased mRNA encoding TNFα and MCP1. Moreover, saturated fat-induced NFκB signaling and elevation of TNFα and MCP1 mRNA in HepG2 cells was blocked by targeted knockdown of S1P receptor 1, supporting a role for this lipid signaling pathway in inflammation in nonalcoholic fatty liver disease.
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