Metabolomics and Lipidomics Study of Mouse Models of Type 1 Diabetes Highlights Divergent Metabolism in Purine and Tryptophan Metabolism Prior to Disease Onset.
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Authors
Murfitt, Steven A
Zaccone, Paola
Wang, Xinzhu
Sawyer, Yvonne
Publication Date
2018-03Journal Title
Journal of proteome research
ISSN
1535-3893
Volume
17
Issue
3
Pages
946-960
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
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Murfitt, S. A., Zaccone, P., Wang, X., Acharjee, A., Sawyer, Y., Koulman, A., Roberts, L. D., et al. (2018). Metabolomics and Lipidomics Study of Mouse Models of Type 1 Diabetes Highlights Divergent Metabolism in Purine and Tryptophan Metabolism Prior to Disease Onset.. Journal of proteome research, 17 (3), 946-960. https://doi.org/10.1021/acs.jproteome.7b00489
Abstract
With the increase in incidence of type 1 diabetes (T1DM), particularly in Westernised societies, there is an urgent need to understand the early molecular and metabolic alterations that accompany the autoimmune disease. This is not least because in murine models early intervention can prevent the development of overt disease. In this study we have applied a liquid chromatography (LC-) and gas chromatography (GC-) mass spectrometry (MS) metabolomics and lipidomics analysis of blood plasma and pancreas tissue extracts to follow the progression of disease in three models related to autoimmune diabetes: the non-obese diabetic (NOD) mouse, which is susceptible to the development of autoimmune diabetes, and the NOD-E (transgenic NOD mice that express the I-E heterodimer of the major histocompatibility complex II) and NOD- severe combined immunodeficiency (SCID) mouse strains, two models protected from the development of diabetes. All three analyses highlighted the metabolic differences between the NOD-SCID mouse and the other two strains, regardless of diabetic status. Comparing between the NOD and NOD-E mice we show the development of T1DM in the NOD mouse is associated with changes in lipid, purine and tryptophan metabolism, including an increase in kynurenic acid and a decrease in lysophospholipids, metabolites previously associated with inflammation.
Keywords
Islets of Langerhans, Animals, Mice, Inbred NOD, Mice, Transgenic, Mice, Mice, SCID, Diabetes Mellitus, Type 1, Prediabetic State, Disease Models, Animal, Kynurenic Acid, Purines, Lysophospholipids, Tryptophan, Histocompatibility Antigens Class II, Chromatography, Liquid, Discriminant Analysis, Autoimmunity, Gene Expression, Principal Component Analysis, Female, Lipid Metabolism, Gas Chromatography-Mass Spectrometry, Metabolomics, Protein Multimerization
Sponsorship
MRC (G0801841)
MRC (MR/P011705/1)
BBSRC (BB/M027252/2)
BBSRC (via European Molecular Biology Laboratory (EMBL)) (BB/L024152/1)
Biotechnology and Biological Sciences Research Council (BB/M027252/1)
BBSRC (BB/P028195/1)
Identifiers
External DOI: https://doi.org/10.1021/acs.jproteome.7b00489
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279970
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