Metabolomics and Lipidomics Study of Mouse Models of Type 1 Diabetes Highlights Divergent Metabolism in Purine and Tryptophan Metabolism Prior to Disease Onset

Steven A Murfitt, Paola Zaccone, Xinzhu Wang, Animesh Acharjee, Yvonne Sawyer, Albert Koulman, Lee D Roberts, Anne Cooke, Julian Leether Griffin

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

With the increase in incidence of type 1 diabetes (T1DM), 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 disease. We have applied a liquid chromatography (LC-) and gas chromatography (GC-) mass spectrometry (MS) metabolomics and lipidomics analysis of blood plasma and pancreas tissue to follow the progression of disease in three models related to autoimmune diabetes: the nonobese diabetic (NOD) mouse, 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 indicating that NOD-SCID mice are poor controls for metabolic changes in NOD mice. By comparing NOD and NOD-E mice, we show the development of T1DM in NOD mice 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.

Original languageEnglish
Pages (from-to)946-960
Number of pages15
JournalJournal of Proteome Research
Volume17
Issue number3
Early online date12 Feb 2018
DOIs
Publication statusPublished - 2 Mar 2018

Keywords

  • Animals
  • Autoimmunity
  • Chromatography, Liquid
  • Diabetes Mellitus, Type 1/immunology
  • Discriminant Analysis
  • Disease Models, Animal
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Gene Expression
  • Histocompatibility Antigens Class II/genetics
  • Islets of Langerhans/immunology
  • Kynurenic Acid/metabolism
  • Lipid Metabolism
  • Lysophospholipids/metabolism
  • Metabolomics/methods
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Prediabetic State/immunology
  • Principal Component Analysis
  • Protein Multimerization
  • Purines/metabolism
  • Tryptophan/metabolism

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