期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep25573
关键词
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资金
- Swiss National Science Foundation [PP00P2_157547, 31003AB_131087]
- Fondation Emma Muschamp
- Centre d'Imagerie BioMedicale (CIBM) of the UNIL
- Centre d'Imagerie BioMedicale (CIBM) of the UNIGE
- Centre d'Imagerie BioMedicale (CIBM) of the HUG
- Centre d'Imagerie BioMedicale (CIBM) of the CHUV
- Centre d'Imagerie BioMedicale (CIBM) of the EPFL
- Leenaards Foundation
- Jeantet Foundation
- CPRIT [RP-101243]
- NIH [5 R37 HL34557, R21EB016197]
- NIH-NIBIB [5 P41 EB015908]
- Swiss National Science Foundation (SNF) [31003AB_131087, PP00P2_157547] Funding Source: Swiss National Science Foundation (SNF)
Cardiac dysfunction is often associated with a shift in substrate preference for ATP production. Hyperpolarized (HP) C-13 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-C-13]pyruvate and [1-C-13]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 [C-13] bicarbonate (-48%), [1-C-13]acetylcarnitine (+113%), and [5-C-13]glutamate (-63%), following fasting. Butyrate uptake was unaffected by fasting, as indicated by [1-C-13]butyrylcarnitine. Mitochondrial pseudoketogenesis facilitated the labeling of the ketone bodies [1-C-13]acetoacetate and [1-C-13]beta-hydroxybutyryate, without evidence of true ketogenesis. HP [1-C-13]acetoacetate was increased in fasting (250%) but decreased during pyruvate co-injection (-82%). Combining HP C-13 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.
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