Circulating sphingolipid biomarkers in models of type 1 diabetes
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 unexplore...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2011-03-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520409319 |
| _version_ | 1818899287728193536 |
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| author | Todd E. Fox Maria C. Bewley Kellee A. Unrath Michelle M. Pedersen Robert E. Anderson Dae Young Jung Leonard S. Jefferson Jason K. Kim Sarah K. Bronson John M. Flanagan Mark Kester |
| author_facet | Todd E. Fox Maria C. Bewley Kellee A. Unrath Michelle M. Pedersen Robert E. Anderson Dae Young Jung Leonard S. Jefferson Jason K. Kim Sarah K. Bronson John M. Flanagan Mark Kester |
| author_sort | Todd E. Fox |
| collection | DOAJ |
| description | 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 Ins2Akita 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. 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. |
| first_indexed | 2024-12-19T19:45:34Z |
| format | Article |
| id | doaj.art-8a4d67730754453aa9e83d6fb506242a |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-19T19:45:34Z |
| publishDate | 2011-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-8a4d67730754453aa9e83d6fb506242a2022-12-21T20:08:09ZengElsevierJournal of Lipid Research0022-22752011-03-01523509517Circulating sphingolipid biomarkers in models of type 1 diabetesTodd E. Fox0Maria C. Bewley1Kellee A. Unrath2Michelle M. Pedersen3Robert E. Anderson4Dae Young Jung5Leonard S. Jefferson6Jason K. Kim7Sarah K. Bronson8John M. Flanagan9Mark Kester10Departments of Pharmacology, Cellular & Molecular Physiology, Milton S. Hershey Medical Center, Hershey, PA; Departments of Biochemistry and Molecular Biology, Milton S. Hershey Medical Center, Hershey, PADepartments of Penn State College of Medicine, Milton S. Hershey Medical Center, Hershey, PADepartments of Pharmacology, Cellular & Molecular Physiology, Milton S. Hershey Medical Center, Hershey, PADepartments of Pharmacology, Cellular & Molecular Physiology, Milton S. Hershey Medical Center, Hershey, PADean A. McGee Eye Institute and Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OKDepartments of Biochemistry and Molecular Biology, Milton S. Hershey Medical Center, Hershey, PADepartments of Biochemistry and Molecular Biology, Milton S. Hershey Medical Center, Hershey, PADepartments of Biochemistry and Molecular Biology, Milton S. Hershey Medical Center, Hershey, PADepartments of Biochemistry and Molecular Biology, Milton S. Hershey Medical Center, Hershey, PADepartments of Penn State College of Medicine, Milton S. Hershey Medical Center, Hershey, PATo whom correspondence should be addressed. mkester@psu.edu; Departments of Pharmacology, Cellular & Molecular Physiology, Milton S. Hershey Medical Center, Hershey, PAAlterations 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 Ins2Akita 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. 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.http://www.sciencedirect.com/science/article/pii/S0022227520409319nervonic acidsphingosine-1-phosphateceramidesphingomyelincerebrosideslipidomics |
| spellingShingle | Todd E. Fox Maria C. Bewley Kellee A. Unrath Michelle M. Pedersen Robert E. Anderson Dae Young Jung Leonard S. Jefferson Jason K. Kim Sarah K. Bronson John M. Flanagan Mark Kester Circulating sphingolipid biomarkers in models of type 1 diabetes Journal of Lipid Research nervonic acid sphingosine-1-phosphate ceramide sphingomyelin cerebrosides lipidomics |
| title | Circulating sphingolipid biomarkers in models of type 1 diabetes |
| title_full | Circulating sphingolipid biomarkers in models of type 1 diabetes |
| title_fullStr | Circulating sphingolipid biomarkers in models of type 1 diabetes |
| title_full_unstemmed | Circulating sphingolipid biomarkers in models of type 1 diabetes |
| title_short | Circulating sphingolipid biomarkers in models of type 1 diabetes |
| title_sort | circulating sphingolipid biomarkers in models of type 1 diabetes |
| topic | nervonic acid sphingosine-1-phosphate ceramide sphingomyelin cerebrosides lipidomics |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520409319 |
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