Print Email Facebook Twitter Identification of prognostic and diagnostic biomarkers of glucose intolerance in ApoE3Leiden mice Title Identification of prognostic and diagnostic biomarkers of glucose intolerance in ApoE3Leiden mice Author Wopereis, S. Radonjic, M. Rubingh, C. van Erk, M. Smilde, A. van Duyvenvoorde, W. Cnubben, N. Kooistra, T. van Ommen, B. Kleemann, R. Publication year 2012 Abstract The prevalence of diabetes mellitus Type 2 could be significantly reduced by early identification of subjects at risk, allowing for better prevention and earlier treatment. Glucose intolerance (GI) is a hallmark of the prediabetic stage. This study aims at identifying 1) prognostic biomarkers predicting the risk of developing GI later in life and 2) diagnostic biomarkers reflecting the degree of already manifest GI. To this end, disease development was followed over time in mice, and biomarkers were identified using lipidomics and transcriptomics. Young adult ApoE3Leiden mice were treated a highfat diet for 12 wk to induce GI. Blood was collected before and during disease development. The individual extent of GI was determined with a glucose tolerance test and the area under the curve (AUC) was calculated for each animal. Subject-specific AUC values were correlated to the plasma lipidome (t = 0) and the white blood cell (WBC) transcriptome (t = 0, 6, and 12 wk) to identify prognostic and diagnostic biomarkers, respectively. The plasma ratio of specific free fatty acids prior to high-fat feeding (C16:1/C16:0, C18:1/C18:0 and C18:2/C22:6) was significantly correlated with the AUC and predictive for future GI. Subsequently, the expression level of specific WBC genes (Acss2, Arfgap1, Tfrc, Cox6b2, Barhl2, Abcb4, Cyp4b1, Sars2, Fgf16, and Tceal8) reflected the individual degree of GI during disease progression. Specific plasma free fatty acids as well as their ratio can be used to predict future GI. The expression levels of specific WBC genes can serve as easy accessible markers to diagnose and monitor already existing GI. © 2012 by the American Physiological Society. Chemicals/CAS: cytochrome P450 2B1, 330207-10-8 Subject LifeMSB - Microbiology and Systems Biology MHR - Metabolic Health Research PHS - Pharmacokinetics & Human Studies RAPID - Risk Analysis for Products in DevelopmentEELS - Earth, Environmental and Life SciencesHealthy for LifeBiologyHealthy LivingDiabetes mellitus Type 2Diabetes mellitus Type 2-prone transgenic ApoE3Leiden micePlasma lipidomicsWhite blood cell transcriptomicsacyl coA synthetase short chain family member 2adp ribosylation factor gtaase activating protein 1atp binding cassette subfamily b proteinbiological markercytochrome c oxidase subunit vib polypeptide 2cytochrome P450 2B1fatty acidfibroblast growth factor 16lipidomeseryl aminoacyl tRNA synthetase 2transcription elongation factor a like 8 proteintranscriptometransferrin receptorunclassified druganimal cellanimal experimentanimal modelarea under the curvearticleblood analysiscontrolled studydisease coursegene expressionglucose intoleranceglucose tolerance testleukocytelipid blood levellipid dietlipidomicsmousenonhumanpredictionpriority journalprognosisprotein analysistranscriptomics To reference this document use: http://resolver.tudelft.nl/uuid:3ac341f1-b64a-415e-b9b9-98d7ef7e568c DOI https://doi.org/10.1152/physiolgenomics.00072.2011 TNO identifier 447262 ISSN 1094-8341 Source Physiological Genomics, 44 (5), 293-304 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.