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Plasma Metabolomics Reveal Longitudinal Changes in Branched‐Chain Amino Acids and other Metabolites during Diabetes Progression in the UCD‐Type‐2‐Diabetes Rat Model
Author(s) -
Piccolo Brian,
Graham James,
Fiehn Oliver,
Havel Peter,
Adams Sean
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.275.4
Subject(s) - diabetes mellitus , medicine , endocrinology , type 2 diabetes , amino acid , metabolomics , leucine , catabolism , valine , metabolome , chemistry , metabolism , biology , biochemistry , metabolite , bioinformatics
Type 2 diabetes mellitus (T2D) causes dysregulation in many metabolic pathways; however, temporal progression of these disturbances has not been fully elucidated. Alterations of branched‐chain amino acids (BCAAs) have been implicated in the diabetes phenotype, but cause‐effect is not established. Using a model that closely resembles T2D in humans, the UCD‐T2DM rat, we utilized metabolomics to assess plasma metabolites in pre‐diabetic rats and after the onset of diabetes at 2‐, 12, and 24 weeks. Partial least squares‐discriminant analysis (PLS‐DA) identified a high number of amino acids that were decreased in plasma at 12‐ and 24‐weeks relative to pre‐diabetic rats. Increased leucine and isoleucine plasma abundances were identified in 24 week diabetic rats only. Plasma BCAAs were inversely related to the decline in the total body weight as diabetes progressed over time. All other amino acids decreased in parallel with the decline in total body weight. TCA cycle intermediates, phenols and glucose derivatives were increased by diabetes at 12‐ and 24‐weeks. These observations indicate that the association between plasma BCAAs and T2D is apparent after the onset of the disease phenotype; thus, a result of T2D. Associations between amino acids and weight suggest that the plasma amino acid profile tracks catabolic changes associated with T2D. Additional metabolites that may provide biomarkers of diabetes progression will also be presented.