The pathological role of adipose derived fatty acids following myocardial infarction has long been hypothesized. However, most methods for reducing adipocyte lipolysis have significant non-adipose effects. Atglistatin, a direct inhibitor of the initial lipase in the lipolysis cascade, has been recently shown to inhibit adipose tissue lipolysis after oral administration. To explore the ability of Atglistatin to impact the pathophysiology of cardiac ischemia we performed prophylactic treatment of mice with Atglistatin for 2 days before 1-hour cardiac ischemia. After 7 days of reperfusion, hearts of Atglistatin treated mice showed significantly improved systolic pump function while infarct and scar size were unaffected. Strain analysis of echocardiographic data revealed an enhanced performance of the remote myocardium as cause for overall improved systolic function. The present study provides evidence that inhibition of adipocyte adipose triglyceride lipase (ATGL) using Atglistatin is able to improve cardiac function after MI by targeting the remote myocardium.

长期以来一直假设心肌梗塞后脂肪衍生的脂肪酸的病理作用。然而，大多数减少脂肪细胞脂肪分解的方法都具有显着的非脂肪作用。Atglistatin 是脂解级联中初始脂肪酶的直接抑制剂，最近已被证明可抑制口服给药后的脂肪组织脂解。为了探索 Atglistatin 影响心脏缺血病理生理学的能力，我们在 1 小时心脏缺血前用 Atglistatin 对小鼠进行了 2 天的预防性治疗。再灌注 7 天后，阿格列汀治疗小鼠的心脏显示出明显改善的收缩泵功能，而梗塞和疤痕大小不受影响。超声心动图数据的应变分析显示远端心肌的性能增强是整体改善收缩功能的原因。本研究提供的证据表明，使用 Atglistatin 抑制脂肪细胞脂肪甘油三酯脂肪酶 (ATGL) 能够通过靶向远端心肌来改善 MI 后的心脏功能。