ArticleThe Journal of biological chemistry2013
Sphingosine kinase 1 is regulated by peroxisome proliferator-activated receptor α in response to free fatty acids and is essential for skeletal muscle interleukin-6 production and signaling in diet-induced obesity.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 47 citations in OpenAlex.
- Aerobic Exercise Activates S1PR1 Signaling in Tumor Endothelial Cells to Promote Vascular Function in Pancreatic Cancer.Cancer research · 2026Article
- Sphingolipids and Atherosclerosis.Current atherosclerosis reports · 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
- Machine learning models to identify lead compound and substitution optimization to have derived energetics and conformational stability through docking and MD simulations for sphingosine kinase 1.Molecular diversity · 2025Article
- Adipocyte sphingosine kinase 1 regulates histone modifiers to disrupt circadian function.bioRxiv : the preprint server for biology · 2024Article
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives.Peptides · 2024Review
- Sphingosine 1-Phosphate Regulates Obesity and Glucose Homeostasis.International journal of molecular sciences · 2024Review
- 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
- Article
- Jiangtang Sanhao formula ameliorates skeletal muscle insulin resistanceFrontiers in pharmacology · 2022Article
- Breast Meat Fatty Acid Profiling and Proteomic Analysis of Beijing-You Chicken During the Laying Period.Frontiers in veterinary science · 2022Article
- Sphingolipids in metabolic disease: The good, the bad, and the unknown.Cell metabolism · 2021Review
- Bioactive sphingolipids: Advancements and contributions from the laboratory of Dr. Lina M. Obeid.Cellular signalling · 2021Review
- Targeting sphingosine kinase 1 (SK1) enhances oncogene-induced senescence through ceramide synthase 2 (CerS2)-mediated generation of very-long-chain ceramides.Cell death & disease · 2021Article
- Depletion of adipocyte sphingosine kinase 1 leads to cell hypertrophy, impaired lipolysis, and nonalcoholic fatty liver disease.Journal of lipid research · 2020Article
- Article
- Sphingosine kinase 1 is required for myristate-induced TNFα expression in intestinal epithelial cells.Prostaglandins & other lipid mediators · 2020Article
- Review
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6 authors at 4 institutions in 1 country.
Funding
Abstract
We previously demonstrated that sphingosine kinase 1 (Sphk1) expression and activity are up-regulated by exogenous palmitate (PAL) in a skeletal muscle model system and in diet-induced obesity in mice; however, potential functions and in vivo relevance of this have not been addressed. Here, we aimed to determine the mechanism by which PAL regulates SphK1 in muscle, and to determine potential roles for its product, sphingosine-1-phosphate (S1P), in muscle biology in the context of obesity. Cloning and analysis of the mouse Sphk1 promoter revealed a peroxisome proliferator-activated receptor (PPAR) α cis-element that mediated activation of a reporter under control of the Sphk1 promoter; direct interaction of PPARα was demonstrated by chromatin immunoprecipitation. PAL treatment induced the proinflammatory cytokine interleukin (IL)-6 in a manner dependent on SphK1, and this was attenuated by inhibition of the sphingosine-1-phosphate receptor 3 (S1PR3). Diet-induced obesity in mice demonstrated that IL-6 expression in muscle, but not adipose tissue, increased in obesity, but this was attenuated in Sphk1(-/-) mice. Moreover, plasma IL-6 levels were significantly decreased in obese Sphk1(-/-) mice relative to obese wild type mice, and muscle, but not adipose tissue IL-6 signaling was activated. These data indicate that PPARα regulates Sphk1 expression in the context of fatty acid oversupply and links PAL to muscle IL-6 production. Moreover, this function of SphK1 in diet-induced obesity suggests a potential role for SphK1 in obesity-associated pathological outcomes.
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