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Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet

Kowalski,GM, Kloehn,J, Burch,ML, Selathurai,A, Hamley,S, Bayol,SAM, Lamon,S, Watt,MJ, Lee-Young,RS, McConville,MJ and Bruce, CR 2015, Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet, Biochimica et Biophysica Acta (BBA)- molecular and cell biology of lipids, vol. 1851, no. 2, pp. 210-219, doi: 10.1016/j.bbalip.2014.12.002.

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Title Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet
Author(s) Kowalski,GMORCID iD for Kowalski,GM orcid.org/0000-0002-1599-017X
Kloehn,J
Burch,ML
Selathurai,A
Hamley,S
Bayol,SAM
Lamon,SORCID iD for Lamon,S orcid.org/0000-0002-3271-6551
Watt,MJ
Lee-Young,RS
McConville,MJ
Bruce, CRORCID iD for Bruce, CR orcid.org/0000-0002-0515-3343
Journal name Biochimica et Biophysica Acta (BBA)- molecular and cell biology of lipids
Volume number 1851
Issue number 2
Start page 210
End page 219
Total pages 10
Publisher Elsevier BV
Place of publication Amsterdam, Netherlands
Publication date 2015-02
ISSN 1388-1981
Keyword(s) Ceramide
Diacylglycerol
Glucose tolerance
Liver
Sphingosine kinase 1
Triacylglycerol
Summary  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.
Language eng
DOI 10.1016/j.bbalip.2014.12.002
Field of Research 060603 Animal Physiology - Systems
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Grant ID NHMRC 1023570
Copyright notice ©2015, Elsevier BV
Persistent URL http://hdl.handle.net/10536/DRO/DU:30069040

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