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


Type
Article
Change log
Authors
Bastiaansen, Jessica AM 
Couturier, Dominique  ORCID logo  https://orcid.org/0000-0001-5774-5036
Gruetter, Rolf 
Yoshihara, Hikari AI  ORCID logo  https://orcid.org/0000-0002-3274-7147
Abstract

Hyperpolarized [1-13C]pyruvate enables direct in vivo assessment of real-time liver enzymatic activities by 13C 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 [1-13C]pyruvate administered at two- to three-fold the basal plasma concentration. The flux through pyruvate dehydrogenase, assessed by 13C-labeling of bicarbonate in the fed condition, was found to be saturated or partially inhibited by supraphysiological doses of hyperpolarized [1-13C]pyruvate. The [13C]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 [13C]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 [1-13C]pyruvate.

Description

Funder: EC | EC Seventh Framework Programm | FP7 People: Marie-Curie Actions (FP7-PEOPLE - Specific Programme "People" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011264; Grant(s): 264780

Keywords
Article, /692/4020/4021/288/2032, /692/308/2778, /631/45/320, /631/1647/245/1628, /59/57, /82/58, /82/6, article
Journal Title
Commun Biol
Conference Name
Journal ISSN
2399-3642
2399-3642
Volume Title
5
Publisher
Springer Science and Business Media LLC
Sponsorship
European Commission (264780)
European Research Council (682574)
Swiss National Science Foundation (133562)