Circulating sphingolipid biomarkers in models of type 1 diabetes

被引：122
作者：
Fox, Todd E. [1 ,2 ]
Bewley, Maria C. [3 ]
Unrath, Kellee A. [1 ]
Pedersen, Michelle M. [1 ]
Anderson, Robert E. [4 ,5 ]
Jung, Dae Young [2 ]
Jefferson, Leonard S. [2 ]
Kim, Jason K. [2 ]
Bronson, Sarah K. [2 ]
Flanagan, John M. [3 ]
Kester, Mark [1 ]
机构：
[1] Penn State Coll Med, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA
[2] Penn State Coll Med, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol, Hershey, PA USA
[3] Penn State Coll Med, Milton S Hershey Med Ctr, Dept Biochem & Mol Biol, Hershey, PA USA
[4] Univ Oklahoma, Hlth Sci Ctr, Dean A McGee Eye Inst, Oklahoma City, OK USA
[5] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA
来源：
JOURNAL OF LIPID RESEARCH | 2011年 / 52卷 / 03期
关键词：
nervonic acid; sphingosine-1-phosphate; ceramide; sphingomyelin; cerebrosides; lipidomics; TANDEM MASS-SPECTROMETRY; INSULIN-RESISTANCE; RECEPTOR SUBTYPES; ADIPOSE-TISSUE; NERVONIC ACID; OBESITY; MICE; METABOLISM; ACTIVATION; ACCUMULATION;
D O I：
10.1194/jlr.M010595
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Alterations in lipid metabolism may contribute to diabetic complications. Sphingolipids are essential components of cell membranes and have essential roles in homeostasis and in the initiation and progression of disease. However, the role of sphingolipids in type 1 diabetes remains largely unexplored. Therefore, we sought to quantify sphingolipid metabolites by LC-MS/MS from two animal models of type 1 diabetes (streptozotocin-induced diabetic rats and Ins2(Akita) diabetic mice) to identify putative therapeutic targets and biomarkers. The results reveal that sphingosine-1-phosphate (So1P) is elevated in both diabetic models in comparison to respective control animals. In addition, diabetic animals demonstrated reductions in plasma levels of omega-9 24:1 (nervonic acid)-containing ceramide, sphingomyelin, and cerebrosides. Reduction of 24:1-esterfied sphingolipids was also observed in liver and heart. Nutritional stress via a high-fat diet also reduced 24:1 content in the plasma and liver of mice, exacerbating the decrease in some cases where diabetes was also present. Subcutaneous insulin corrected both circulating So1P and 24:1 levels in the murine diabetic model.jlr Thus, changes in circulating sphingolipids, as evidenced by an increase in bioactive So1P and a reduction in cardio-and neuro-protective omega-9 esterified sphingolipids, may serve as biomarkers for type 1 diabetes and represent novel therapeutic targets.-Fox, T. E., M. C. Bewley, K. A. Unrath, M. M. Pedersen, R. E. Anderson, D. Y. Jung, L. S. Jefferson, J. K. Kim, S. K. Bronson, J. M. Flanagan, and M. Kester. Circulating sphingolipid biomarkers in models of type 1 diabetes. J. Lipid Res. 2011. 52: 509-517.
引用
收藏
页码：509 / 517
页数：9
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