Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet
| Autor: | Joachim Kloehn, Malcolm J. McConville, Ahrathy Selathurai, Stephanie A.M. Bayol, Séverine Lamon, Robert S. Lee-Young, Matthew J. Watt, Grzegorz M Kowalski, Micah L Burch, Clinton R. Bruce, Steven Hamley |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Ceramide Time Factors Sphingosine kinase Ceramides Diet High-Fat chemistry.chemical_compound Insulin resistance Dietary Sucrose Internal medicine medicine Animals Homeostasis RNA Messenger Diet Fat-Restricted Molecular Biology Triglycerides Diacylglycerol kinase Glucose tolerance test medicine.diagnostic_test biology Cell Biology Lipid signaling medicine.disease Dietary Fats Up-Regulation Mice Inbred C57BL Phosphotransferases (Alcohol Group Acceptor) SPHK2 Glucose Endocrinology Liver Sphingosine kinase 1 chemistry biology.protein lipids (amino acids peptides and proteins) |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1851:210-219 |
| ISSN: | 1388-1981 |
| DOI: | 10.1016/j.bbalip.2014.12.002 |
| Popis: | Hepatic insulin resistance is a major risk factor for the development of type 2 diabetes and is associated with the accumulation of lipids, including diacylglycerol (DAG), triacylglycerols (TAG) and ceramide. There is evidence that enzymes involved in ceramide or sphingolipid metabolism may have a role in regulating concentrations of glycerolipids such as DAG and TAG. Here we have investigated the role of sphingosine kinase (SphK) in regulating hepatic lipid levels. We show that mice on a high-fat high-sucrose diet (HFHS) displayed glucose intolerance, elevated liver TAG and DAG, and a reduction in total hepatic SphK activity. Reduced SphK activity correlated with downregulation of SphK1, but not SphK2 expression, and was not associated with altered ceramide levels. The role of SphK1 was further investigated by overexpressing this isoform in the liver of mice in vivo. On a low-fat diet (LFD) mice overexpressing liver SphK1, displayed reduced hepatic TAG synthesis and total TAG levels, but with no change to DAG or ceramide. These mice also exhibited no change in gluconeogenesis, glycogenolysis or glucose tolerance. Similarly, overexpression of SphK1 had no effect on the pattern of endogenous glucose production determined during a glucose tolerance test. Under HFHS conditions, normalization of liver SphK activity to levels observed in LFD controls did not alter hepatic TAG concentrations. Furthermore, DAG, ceramide and glucose tolerance were also unaffected. In conclusion, our data suggest that SphK1 plays an important role in regulating TAG metabolism under LFD conditions. |
| Databáze: | OpenAIRE |
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