Bastiaansen Jessica A M, Merritt Matthew E, Comment Arnaud
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.
Sci Rep. 2016 May 6;6:25573. doi: 10.1038/srep25573.
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.
心脏功能障碍通常与ATP生成的底物偏好转变有关。超极化（HP）（13）C磁共振波谱（MRS）具有高灵敏度和特异性，因而具备在体内检测实时代谢变化的独特能力。本文采用一种使用HP [1-（13）C]丙酮酸和[1-（13）C]丁酸的方案来测量体内碳水化合物与脂肪酸代谢。在尾静脉注射后，于9.4T磁场下研究了喂食和禁食的Sprague Dawley大鼠（n = 36）的代谢变化。丙酮酸和丁酸竞争乙酰辅酶A的生成，禁食后[（13）C]碳酸氢盐（-48%）、[1-（13）C]乙酰肉碱（+113%）和[5-（13）C]谷氨酸（-63%）的显著变化证明了这一点。如[1-（13）C]丁酰肉碱所示，禁食不影响丁酸摄取。线粒体假酮生成促进了酮体[1-（13）C]乙酰乙酸和[1-（13）C]β-羟基丁酸的标记，但无真正酮生成的证据。HP [1-（13）C]乙酰乙酸在禁食时增加（250%），但在丙酮酸共同注射期间减少（-82%）。结合HP （13）C技术和单独成像剂的共同给药能够无创且同时监测脂肪酸和碳水化合物氧化。该方案阐述了一种同时评估通过不同酶途径的代谢通量的新方法，并能够对常与疾病相关的心肌能量变化进行机制研究。
