Academic Journal
Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet
| العنوان: | Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet |
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| المؤلفون: | Greg Kowalski, Joachim Kloehn, Micah L Burch, Ahrathy Selathurai, Steven Hamley, Stéphanie AM Bayol, Severine Lamon, Matthew J Watt, Robert S Lee-Young, Malcolm J McConville, Clinton Bruce |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Centre for Physical Activity & Nutrition Research, School of Exercise and Nutrition Sciences, NHMRC 1023570, 920104 Diabetes, 970111 Expanding Knowledge in the Medical and Health Sciences, 060603 Animal Physiology - Systems |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | http://hdl.handle.net/10536/DRO/DU:30069040 |
| الاتاحة: | http://hdl.handle.net/10536/DRO/DU:30069040 https://figshare.com/articles/journal_contribution/Overexpression_of_sphingosine_kinase_1_in_liver_reduces_triglyceride_content_in_mice_fed_a_low_but_not_high-fat_diet/20918122 |
| Rights: | All Rights Reserved |
| رقم الانضمام: | edsbas.8DD30D7F |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |