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NMR metabolomics identifies over 60 biomarkers associated with Type II Diabetes impairment in db/db mice

Mora-Ortiz, M., Nuñez Ramos, P., Oregioni, A. and Claus, S. P. (2019) NMR metabolomics identifies over 60 biomarkers associated with Type II Diabetes impairment in db/db mice. Metabolomics, 15 (6). 89. ISSN 1573-3890

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To link to this item DOI: 10.1007/s11306-019-1548-8

Abstract/Summary

The rapid expansion of Type 2 Diabetes (T2D), that currently affects 90% of people suffering from diabetes, urges us to develop a better understanding of the metabolic processes involved in the disease process in order to develop better therapies. The most commonly used model for T2D research is the db/db (BKS.Cg-Dock7 < m > +/+ Lepr < db >/J) mouse model. Yet, a systematic H NMR based metabolomics characterisation of most tissues in this animal model has not been published. Here, we provide a systematic organ-specific metabolomics analysis of this widely employed model using NMR spectroscopy. The aim of this study was to characterise the metabolic modulations associated with T2D in db/db mice in 18 relevant biological matrices. High-resolution H-NMR and 2D-NMR spectroscopy were applied to 18 biological matrices of 12 db/db mice (WT control n = 6, db/db = 6) aged 22 weeks, when diabetes is fully established. 61 metabolites associated with T2D were identified. Kidney, spleen, eye and plasma were the biological matrices carrying the largest metabolomics modulations observed in established T2D, based on the total number of metabolites that showed a statistical difference between the diabetic and control group in each tissue (16 in each case) and the strength of the O-PLS DA model for each tissue. Glucose and glutamate were the most commonly associated metabolites found significantly increased in nine biological matrices. Investigated sections where no increase of glucose was associated with T2D include all intestinal segments (i.e. duodenum, jejunum, ileum and colon). Microbial co-metabolites such as acetate and butyrate, used as carbon sources by the host, were identified in excess in the colonic tissues of diabetic individuals. The metabolic biomarkers identified using H NMR-based metabolomics will represent a useful resource to explore metabolic pathways involved in T2D in the db/db mouse model.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Human Nutrition Research Group
ID Code:84471
Uncontrolled Keywords:Metabolome, Nuclear magnetic resonance (NMR) spectroscopy, Type II Diabetes, db/db mouse
Publisher:Springer

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