[ 13 C]bicarbonate labelled from hyperpolarized [1- 13 C]pyruvate is an in vivo marker of hepatic gluconeogenesis in fasted state.

Autor: Can E; Institute of Physics, Ecole Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland., Bastiaansen JAM; Institute of Physics, Ecole Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland.; Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Couturier DL; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, Cambridgeshire, CB2 0RE, UK., Gruetter R; Institute of Physics, Ecole Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland., Yoshihara HAI; Institute of Physics, Ecole Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland., Comment A; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, Cambridgeshire, CB2 0RE, UK. arnaud.comment@ge.com.; General Electric Healthcare, Chalfont St Giles, Buckinghamshire, HP8 4SP, UK. arnaud.comment@ge.com.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2022 Jan 10; Vol. 5 (1), pp. 10. Date of Electronic Publication: 2022 Jan 10.
DOI: 10.1038/s42003-021-02978-2
Abstrakt: Hyperpolarized [1- 13 C]pyruvate enables direct in vivo assessment of real-time liver enzymatic activities by 13 C magnetic resonance. However, the technique usually requires the injection of a highly supraphysiological dose of pyruvate. We herein demonstrate that liver metabolism can be measured in vivo with hyperpolarized [1- 13 C]pyruvate administered at two- to three-fold the basal plasma concentration. The flux through pyruvate dehydrogenase, assessed by 13 C-labeling of bicarbonate in the fed condition, was found to be saturated or partially inhibited by supraphysiological doses of hyperpolarized [1- 13 C]pyruvate. The [ 13 C]bicarbonate signal detected in the liver of fasted rats nearly vanished after treatment with a phosphoenolpyruvate carboxykinase (PEPCK) inhibitor, indicating that the signal originates from the flux through PEPCK. In addition, the normalized [ 13 C]bicarbonate signal in fasted untreated animals is dose independent across a 10-fold range, highlighting that PEPCK and pyruvate carboxylase are not saturated and that hepatic gluconeogenesis can be directly probed in vivo with hyperpolarized [1- 13 C]pyruvate.
(© 2022. The Author(s).)
Databáze: MEDLINE
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