Hyperpolarized butyrate: a metabolic probe of short chain fatty acid metabolism in the heart.
PURPOSE
Butyrate, a short chain fatty acid, was studied as a novel hyperpolarized substrate for use in dynamic nuclear polarization enhanced magnetic resonance spectroscopy experiments, to define the pathways of short chain fatty acid and ketone body metabolism in real time.


METHODS
Butyrate was polarized via the dynamic nuclear polarization process and subsequently dissolved to generate an injectable metabolic substrate. Metabolism was initially assessed in the isolated perfused rat heart, followed by evaluation in the in vivo rat heart.


RESULTS
Hyperpolarized butyrate was generated with a polarization level of 7% and was shown to have a T1 relaxation time of 20 s. These physical characteristics were sufficient to enable assessment of multiple steps in its metabolism, with the ketone body acetoacetate and several tricarboxylic acid cycle intermediates observed both in vitro and in vivo. Metabolite to butyrate ratios of 0.1-0.4% and 0.5-2% were observed in vitro and in vivo respectively, similar to levels previously observed with hyperpolarized [2-(13) C]pyruvate.


CONCLUSIONS
In this study, butyrate has been demonstrated to be a suitable hyperpolarized substrate capable of revealing multi-step metabolism in dynamic nuclear polarization experiments and providing information on the metabolism of fatty acids not currently achievable with other hyperpolarized substrates.
['Ball|Daniel R|DR|', 'Rowlands|Ben|B|', 'Dodd|Michael S|MS|', 'Le Page|Lydia|L|', 'Ball|Vicky|V|', 'Carr|Carolyn A|CA|', 'Clarke|Kieran|K|', 'Tyler|Damian J|DJ|']
D000818:Animals D002087:Butyrates D002247:Carbon Isotopes D005232:Fatty Acids, Volatile D066298:In Vitro Techniques D007553:Isotope Labeling D008297:Male D015336:Molecular Probe Techniques D009206:Myocardium D066244:Proton Magnetic Resonance Spectroscopy D019275:Radiopharmaceuticals D051381:Rats D017208:Rats, Wistar D014018:Tissue Distribution
hyperpolarization butyrate short chain fatty acids heart dynamic nuclear polarization magnetic resonance spectroscopy ketone bodies