Department of Nuclear Medicine & PET Center, Aarhus University Hospital, Aarhus, Denmark
Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark.
J Am Heart Assoc. 2017 Feb 27;6(3):e005066. doi: 10.1161/JAHA.116.005066.
High levels of ketone bodies are associated with improved survival as observed with regular exercise, caloric restriction, and-most recently-treatment with sodium-glucose linked transporter 2 inhibitor antidiabetic drugs. In heart failure, indices of ketone body metabolism are upregulated, which may improve energy efficiency and increase blood flow in skeletal muscle and the kidneys. Nevertheless, it is uncertain how ketone bodies affect myocardial glucose uptake and blood flow in humans. Our study was therefore designed to test whether ketone body administration in humans reduces myocardial glucose uptake (MGU) and increases myocardial blood flow.
Eight healthy subjects, median aged 60 were randomly studied twice: (1) During 390 minutes infusion of Na-3-hydroxybutyrate (KETONE) or (2) during 390 minutes infusion of saline (SALINE), together with a concomitant low-dose hyperinsulinemic-euglycemic clamp to inhibit endogenous ketogenesis. Myocardial blood flow was measured by O-HO positron emission tomography/computed tomography, myocardial fatty acid metabolism by C-palmitate positron emission tomography/computed tomography and MGU by F-fluorodeoxyglucose positron emission tomography/computed tomography. Similar euglycemia, hyperinsulinemia, and suppressed free fatty acids levels were recorded on both study days; Na-3-hydroxybutyrate infusion increased circulating Na-3-hydroxybutyrate levels from zero to 3.8±0.5 mmol/L. MGU was halved by hyperketonemia (MGU [nmol/g per minute]: 304±97 [SALINE] versus 156±62 [KETONE], <0.01), whereas no effects were observed on palmitate uptake oxidation or esterification. Hyperketonemia increased heart rate by ≈25% and myocardial blood flow by 75%.
Ketone bodies displace MGU and increase myocardial blood flow in healthy humans; these novel observations suggest that ketone bodies are important cardiac fuels and vasodilators, which may have therapeutic potentials.
酮体水平升高与存活率提高有关，这在规律运动、热量限制和最近的钠-葡萄糖共转运蛋白 2 抑制剂抗糖尿病药物治疗中均有观察到。在心衰中，酮体代谢指数上调，这可能提高能量效率并增加骨骼肌和肾脏的血流。然而，酮体如何影响人类心肌葡萄糖摄取和血流尚不确定。因此，我们的研究旨在测试人体给予酮体是否会降低心肌葡萄糖摄取（MGU）并增加心肌血流。
8 名中位年龄 60 岁的健康受试者被随机研究了两次：（1）在 390 分钟的 Na-3-羟丁酸（酮体）输注期间，或（2）在 390 分钟的生理盐水（盐水）输注期间，同时进行低剂量的高胰岛素-正常血糖钳夹以抑制内源性酮体生成。心肌血流通过 O-HO 正电子发射断层扫描/计算机断层扫描测量，心肌脂肪酸代谢通过 C-软脂酸正电子发射断层扫描/计算机断层扫描测量，MGU 通过 F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描测量。在两天的研究中，记录到相似的血糖、高胰岛素血症和抑制游离脂肪酸水平；Na-3-羟丁酸输注使循环中的 Na-3-羟丁酸水平从 0 增加到 3.8±0.5mmol/L。高酮血症使 MGU 减半（MGU [nmol/g/分钟]：304±97 [盐水]与 156±62 [酮体]，<0.01），而棕榈酸摄取氧化或酯化则没有影响。高酮血症使心率增加约 25%，心肌血流增加 75%。
酮体替代了健康人体的 MGU 并增加了心肌血流；这些新的观察结果表明，酮体是重要的心脏燃料和血管扩张剂，可能具有治疗潜力。
Zotero 插件
