Measuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-13 C]butyrate and [1-13C]pyruvate

Jessica A M Bastiaansen, Matthew E. Merritt, Arnaud Comment

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cardiac dysfunction is often associated with a shift in substrate preference for ATP production. Hyperpolarized (HP) 13C magnetic resonance spectroscopy (MRS) has the unique ability to detect real-time metabolic changes in vivo due to its high sensitivity and specificity. Here a protocol using HP [1-13C]pyruvate and [1-13C]butyrate is used to measure carbohydrate versus fatty acid metabolism in vivo. Metabolic changes in fed and fasted Sprague Dawley rats (n = 36) were studied at 9.4 T after tail vein injections. Pyruvate and butyrate competed for acetyl-CoA production, as evidenced by significant changes in [13C]bicarbonate (-48%), [1-13C]acetylcarnitine (+113%), and [5-13C]glutamate (-63%), following fasting. Butyrate uptake was unaffected by fasting, as indicated by [1-13C]butyrylcarnitine. Mitochondrial pseudoketogenesis facilitated the labeling of the ketone bodies [1-13C]acetoacetate and [1-13C]β-hydroxybutyryate, without evidence of true ketogenesis. HP [1-13C]acetoacetate was increased in fasting (250%) but decreased during pyruvate co-injection (-82%). Combining HP 13C technology and co-administration of separate imaging agents enables noninvasive and simultaneous monitoring of both fatty acid and carbohydrate oxidation. This protocol illustrates a novel method for assessing metabolic flux through different enzymatic pathways simultaneously and enables mechanistic studies of the changing myocardial energetics often associated with disease.

Original languageEnglish (US)
Article number25573
JournalScientific Reports
Volume6
DOIs
StatePublished - May 6 2016

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Butyrates
Pyruvic Acid
Fasting
Myocardium
Fatty Acids
Carbohydrates
Acetylcarnitine
Ketone Bodies
Acetyl Coenzyme A
Injections
Aptitude
Bicarbonates
Sprague Dawley Rats
Tail
Glutamic Acid
Veins
Magnetic Resonance Spectroscopy
Adenosine Triphosphate
Technology
Sensitivity and Specificity

ASJC Scopus subject areas

  • General

Cite this

Measuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-13 C]butyrate and [1-13C]pyruvate. / Bastiaansen, Jessica A M; Merritt, Matthew E.; Comment, Arnaud.

In: Scientific Reports, Vol. 6, 25573, 06.05.2016.

Research output: Contribution to journalArticle

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