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13C3‐pyruvate administration revealed differential metabolism between tissues and red blood cells and improved heart function during endotoxemia
Author(s) -
Bateman Ryon Marshall,
Nagahata Yoshiko,
Yukutake Yoshi,
Ohmura Mitsuyo,
Hishiki Takako,
Suematsu Makoto
Publication year - 2011
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.25.1_supplement.1000.17
Subject(s) - metabolism , glycolysis , glycerol , chemistry , medicine , endocrinology , metabolome , gluconeogenesis , carbohydrate metabolism , metabolomics , biochemistry , metabolite , biology , chromatography
The systemic inflammatory response induces a “hypermetabolic” state; yet, metabolic changes are not well understood. We assessed intermediary metabolism by determining glycolytic, TCA and PPP metabolites, amino acids and ATP levels. C57BL/6 mice (30–35g) were injected intraperitoneally with lipopolysaccharide (LPS, 40mg/kg) to induce endotoxemia. Six hours post LPS, 13 C3‐pyruvate was administered subcutaneously and heart, liver and RBCs harvested (20, 40, 60 minutes). 13 C3‐labeled metabolites were measured by capillary electrophoresis ‐ mass spectrometry and quantified by AUC/t0–60. We found RBCs preferentially metabolized 13 C3‐pyruvate compared to heart or liver and were a net lactate source. Under hypoglycemic conditions, RBCs accumulated 13 C3‐glycerol‐3phosphate (red cell glycerol flux remained normal) and 13 C3‐2,3BPG. 13 C3‐glycolytic intermediates increased in the heart and liver, while 13 C3‐TCA intermediates decreased. Amino acids increased in the liver. ATP was stable in the heart, but decreased in the liver and RBCs. Echocardiography revealed a partial recovery of left ventricular function that correlated with shifts in RBC metabolism, suggesting that a possible combination of enhanced RBC function and heart metabolism was beneficial to depressed organ function during the onset of endotoxemia. Support: GCOE Program for Metabolomics Systems Biology, MEXT, Japan.