title: Measuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-(13)C]butyrate and [1-(13)C]pyruvate.
abstract: Cardiac dysfunction is often associated with a shift in substrate preference for ATP production. Hyperpolarized (HP) (13)C 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-(13)C]pyruvate and [1-(13)C]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 [(13)C]bicarbonate (-48%), [1-(13)C]acetylcarnitine (+113%), and [5-(13)C]glutamate (-63%), following fasting. Butyrate uptake was unaffected by fasting, as indicated by [1-(13)C]butyrylcarnitine. Mitochondrial pseudoketogenesis facilitated the labeling of the ketone bodies [1-(13)C]acetoacetate and [1-(13)C]β-hydroxybutyryate, without evidence of true ketogenesis. HP [1-(13)C]acetoacetate was increased in fasting (250%) but decreased during pyruvate co-injection (-82%). Combining HP (13)C 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.
authors.affiliation: Department of Radiology, University Hospital Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.|Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Jessica A M
authors.initials: JA
authors.lastname: Bastiaansen
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Merritt
authors.affiliation: Institute of Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Comment
mesh_terms: D000818:Animals; D020148:Butyric Acid / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D002247:Carbon Isotopes / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D008297:Male; D055442:Metabolome; D009206:Myocardium / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
chemical_list: D002247:Carbon Isotopes; D005227:Fatty Acids; D020148:Butyric Acid; D019289:Pyruvic Acid