BACKGROUND Obesity is strongly associated with exercise intolerance and the development of heart failure. Whereas myocardial energetics and diastolic function are impaired in obesity, systolic function is usually preserved. This suggests that the rate of ATP delivery is maintained, but this has never been explored in human obesity. We hypothesized that ATP transfer rate through creatine kinase (CK) (kfCKrest) would be increased, compensating for depleted energy stores (phosphocreatine/ATP), but potentially limiting greater ATP delivery during increased workload. We hypothesized that these changes would normalize with weight loss. METHODS We recruited 80 volunteers (35 controls [body mass index 24±3 kg/m2], 45 obese [body mass index 35±5 kg/m2]) without coexisting cardiovascular disease. Participants underwent body composition analysis, magnetic resonance imaging of abdominal, liver, and myocardial fat content, left ventricular function, and 31P magnetic resonance spectroscopy to assess phosphocreatine/ATP and CK kinetics, at rest and during dobutamine stress. Obese volunteers were assigned to a dietary weight loss intervention, before reexamination. RESULTS At rest, although myocardial phosphocreatine/ATP was 14% lower in obesity (1.9±0.3 versus 2.2±0.2, P<0.001), kfCkrest was 33% higher (0.23±0.07 s-1 versus 0.16±0.08 s-1, P=0.002), yielding no difference in overall resting ATP delivery (obese 2.5±0.9 µmol·g-1·s-1 versus control 2.2±1.1 µmol·g-1·s-1, P=0.232). In controls, increasing cardiac workload led to an increase in both kfCK (+86%, P<0.001) and ATP delivery (+80%, P<0.001). However, in obesity, similar stress led to no significant increase in either kfCK (P=0.117) or ATP delivery (P=0.608). This was accompanied by reduced systolic augmentation (absolute increase in left ventricular ejection fraction, obese +16±7% versus control +21±4%, P=0.031). Successful weight loss (-11±5% body weight) was associated with improvement of these energetic changes such that there was no significant difference in comparison with controls. CONCLUSIONS In the obese resting heart, the myocardial CK reaction rate is increased, maintaining ATP delivery despite reduced phosphocreatine/ATP. During increased workload, although the nonobese heart increases ATP delivery through CK, the obese heart does not; this is associated with reduced systolic augmentation and exercise tolerance. Weight loss reverses these energetic changes. This highlights myocardial energy delivery through CK as a potential therapeutic target to improve symptoms in obesity-related heart disease, and a fascinating modifiable pathway involved in the progression to heart failure, as well.

中文翻译：

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肥胖症中的心肌能量学：通过肌酸激酶增强 ATP 传递，并抑制应激反应。

背景技术肥胖与运动不耐受和心力衰竭的发展密切相关。虽然肥胖症患者的心肌能量学和舒张功能受损，但收缩功能通常得以保留。这表明 ATP 的传递速率得以维持，但这从未在人类肥胖症中进行过探索。我们假设通过肌酸激酶 (CK) (kfCKrest) 的 ATP 转移率会增加，以补偿耗尽的能量储存（磷酸肌酸/ATP），但可能会在增加的工作量期间限制更多的 ATP 输送。我们假设这些变化会随着体重减轻而正常化。方法 我们招募了 80 名志愿者（35 名对照组 [体重指数 24±3 kg/m2]，45 名肥胖 [体重指数 35±5 kg/m2]），没有并存心血管疾病。参与者接受了身体成分分析，腹部、肝脏和心肌脂肪含量、左心室功能的磁共振成像和 31P 磁共振波谱以评估磷酸肌酸/ATP 和 CK 动力学，在休息和多巴酚丁胺应激期间。在重新检查之前，肥胖的志愿者被分配到饮食减肥干预中。结果 在休息时，虽然肥胖患者的心肌磷酸肌酸/ATP 降低了 14%（1.9±0.3 对 2.2±0.2，P<0.001），但 kfCkrest 升高了 33%（0.23±0.07 s-1 对 0.16±0.08 s-1，P = 0.002），总体静息 ATP 递送没有差异（肥胖 2.5±0.9 µmol·g-1·s-1 与对照组 2.2±1.1 µmol·g-1·s-1，P=0.232）。在对照组中，心脏负荷的增加导致 kfCK（+86%，P<0.001）和 ATP 输送（+80%，P<0.001）的增加。然而，在肥胖症中，类似的压力导致 kfCK 没有显着增加（P = 0. 117) 或 ATP 递送 (P=0.608)。这伴随着收缩期增强减少（左心室射血分数绝对增加，肥胖+16±7% 与对照组+21±4%，P=0.031）。成功的体重减轻（-11±5% 体重）与这些能量变化的改善有关，因此与对照组相比没有显着差异。结论 在肥胖的静息心脏中，心肌 CK 反应率增加，尽管磷酸肌酸/ATP 减少，但仍维持 ATP 输送。在工作量增加期间，虽然非肥胖心脏通过 CK 增加 ATP 输送，但肥胖心脏不会；这与收缩期增强和运动耐量降低有关。减肥逆转了这些精力充沛的变化。