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Fluxome analysis of C13‐pyruvate reveals differential metabolic responses between heart, liver and red blood cells following endotoxemia
Author(s) -
Bateman Ryon M,
Nagahata Yoshiko,
Ohmura Mitsuyo,
Hishiki Takako,
Suematsu Makoto
Publication year - 2010
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.24.1_supplement.889.1
Subject(s) - metabolite , glycolysis , metabolome , metabolomics , chemistry , medicine , pyruvic acid , endocrinology , metabolism , lipopolysaccharide , biochemistry , biology , chromatography
The systemic inflammatory response results in a “hypermetabolic” state; yet, metabolic changes are not clearly understood. The objective was to determine glycolytic, TCA and PPP metabolites, amino acids and ATP levels in heart, liver and red blood cells. C57BL/6 mice (30‐35g) were injected intraperitoneally with lipopolysaccharide (LPS, 40mg/kg). Six hours post LPS, C13‐pyruvate (a key intermediate metabolite) was administered subcutaneously. At 20, 40 and 60 minutes, heart, liver and RBCs were collected. Labeled metabolites were measured using capillary electrophoresis ‐ mass spectrometry, quantified by calculating the AUC/t0‐60 and expressed relative to control. The RBC preferentially metabolized pyruvate (9‐fold increase) compared to heart (1.2‐fold increase) or liver (‐2.1‐fold decrease), and was a net lactate source (2.1‐fold increase). Glycolytic intermediates increased in the heart, but decreased in the RBC, while TCA intermediates decreased in the heart. The liver showed increased amino acids. ATP was stable in heart, but decreased in liver and RBC. Endotoxemia induces differential metabolic responses between tissues. Support: Global COE Program for Metabolomics Systems Biology, MEXT, Japan.