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Metabolite Profiling In Plasma and Tissues of ob/ob ‐/‐ and db/db ‐/‐ Mice Identifies Novel Markers of Obesity and Type 2 Diabetes
Author(s) -
Giesbertz Pieter,
Spanier Britta,
Rein Dietrich,
Daniel Hannelore
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.389.8
Subject(s) - metabolite , adipose tissue , endocrinology , medicine , type 2 diabetes , metabolomics , diabetes mellitus , obesity , leptin , insulin resistance , chemistry , biology , chromatography
Metabolomics approaches in humans have identified around 40 plasma metabolites associated with insulin resistance and type 2 diabetes (T2D). T2D often coincides with obesity. To be able to separate diabetes‐associated from obesity‐associated effects on plasma metabolites we used two mouse models, one with pure obesity ( ob/ob ‐/‐ ) and another with diabetes in addition ( db/db ‐/‐ ). In these mice, we profiled plasma, liver, skeletal muscle and adipose tissue using GC‐MS and LC‐MS/MS. We identified 24 metabolites specifically associated with diabetes but not with obesity. Amongst those known markers such as 1,5‐anhydrosorbitol and 3‐hydroxybutyrate as well as glyoxylate were identified. New metabolites in the diabetic model were lysine, O‐phosphotyrosine, and branched‐chain fatty acids. In addition, we identified 33 metabolites that were similarly altered in both models, represented by branched‐chain amino acids, glycine, serine, pantothenic acid, trans‐4‐hydroxyproline, and a large number of lipids and derivatives. Correlation analyses showed stronger associations for concentrations of amino acids between plasma and adipose tissue in db/db ‐/‐ mice as compared to ob/ob ‐/‐ mice, suggesting an increased role for adipose tissue in the diabetic state. Taken together, by studying mice with metabolite signatures that resemble the metabolic syndrome in the human condition, we have found new metabolite entities that offer starting points for studies in human cohorts.