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Scientific article
English

Hyperpolarized 13C lactate as a substrate for in vivo metabolic studies in skeletal muscle

Contributors

Bastiaansen, Jessica A. M.; Yoshihara, Hikari A. I.; Takado, Yuhei; Gruetter, Rolf; Comment, Arnaud

Published in

Metabolomics, vol. 10, no. 5, p. 986-994

Publication date

2014

Abstract

Resting skeletal muscle has a preference for the oxidation of lipids compared to carbohydrates and a shift towards carbohydrate oxidation is observed with increasing exercise. Lactate is not only an end product in skeletal muscle but also an important metabolic intermediate for mitochondrial oxidation. Recent advances in hyperpolarized MRS allow the measurement of substrate metabolism in vivo in real time. The aim of this study was to investigate the use of hyperpolarized 13C lactate as a substrate for metabolic studies in skeletal muscle in vivo. Carbohydrate metabolism in healthy rat skeletal muscle at rest was studied in different nutritional states using hyperpolarized [1-13C]lactate, a substrate that can be injected at physiological concentrations and leaves other oxidative processes undisturbed. 13C label incorporation from lactate into bicarbonate in fed animals was observed within seconds but was absent after an overnight fast, representing inhibition of the metabolic flux through pyruvate dehydrogenase (PDH). A significant decrease in 13C labeling of alanine was observed comparing the fed and fasted group, and was attributed to a change in cellular alanine concentration and not a decrease in enzymatic flux through alanine transaminase. We conclude that hyperpolarized [1-13C]lactate can be used to study carbohydrate oxidation in resting skeletal muscle at physiological levels. The herein proposed method allows probing simultaneously both PDH activity and variations in alanine tissue concentration, which are associated with metabolic dysfunctions. A simple alteration of the nutritional state demonstrated that the observed pyruvate, alanine, and bicarbonate signals are indeed sensitive markers to probe metabolic changes in vivo.

UNIGE affiliation entities

Citation (ISO format)

BASTIAANSEN, Jessica A. M. et al. Hyperpolarized 13C lactate as a substrate for in vivo metabolic studies in skeletal muscle. In: Metabolomics, 2014, vol. 10, n° 5, p. 986–994. doi: 10.1007/s11306-014-0630-5

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Article (Published version)

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Additional URL for this publication

http://link.springer.com/10.1007/s11306-014-0630-5

Journal ISSN

1573-3882
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Technical informations

Creation

10/01/2015 17:48:00

First validation

10/01/2015 17:48:00

Update

14/03/2023 22:39:46

Status update

14/03/2023 22:39:45

Last indexation

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