College of Nursing and Health Innovation, Department of Kinesiology, University of Texas at Arlington, Arlington, TX, USA.
Biomedical Consulting in MRS, Albuquerque, NM, USA.
J Physiol. 2023 Apr;601(8):1371-1382. doi: 10.1113/JP284272. Epub 2023 Mar 18.
Mounting evidence suggests that myocardial steatosis contributes to left ventricular diastolic dysfunction, but definitive evidence in humans is lacking due to confounding comorbidities. As such, we utilized a 48-h food restriction model to acutely increase myocardial triglyceride (mTG) content - measured by H magnetic resonance spectroscopy - in 27 young healthy volunteers (13 men/14 women). Forty-eight hours of fasting caused a more than 3-fold increase in mTG content (P < 0.001). Diastolic function - defined as early diastolic circumferential strain rate (CSRd) - was unchanged following the 48-h fasting intervention, but systolic circumferential strain rate was elevated (P < 0.001), indicative of systolic-diastolic uncoupling. Indeed, in a separate control experiment in 10 individuals, administration of low-dose dobutamine (2 μg/kg/min) caused a similar change in systolic circumferential strain rate as was found during 48 h of food restriction, along with a proportionate increase in CSRd, such that the two metrics remained coupled. Taken together, these data indicate that myocardial steatosis contributes to diastolic dysfunction by impairing diastolic-systolic coupling in healthy adults, and suggest that steatosis may contribute to the progression of heart disease. KEY POINTS: Preclinical evidence strongly suggests that myocardial lipid accumulation (termed steatosis) is an important mechanism driving heart disease. Definitive evidence in humans is limited due to the confounding influence of multiple underlying comorbidities. Using a 48-h food restriction model to acutely increase myocardial triglyceride content in young healthy volunteers, we demonstrate an association between myocardial steatosis and left ventricular diastolic dysfunction. These data advance the hypothesis that myocardial steatosis may contribute to diastolic dysfunction and suggest myocardial steatosis as a putative therapeutic target.
越来越多的证据表明心肌脂肪变性导致左心室舒张功能障碍，但由于混杂的合并症，人类缺乏明确的证据。因此，我们利用 48 小时禁食模型使 27 名年轻健康志愿者（13 名男性/14 名女性）的心肌甘油三酯（mTG）含量（通过 H 磁共振波谱测量）急性增加。48 小时禁食导致 mTG 含量增加超过 3 倍（P<0.001）。在 48 小时禁食干预后，舒张功能（定义为早期舒张周向应变率（CSRd））保持不变，但收缩周向应变率升高（P<0.001），表明收缩-舒张解偶联。事实上，在 10 名个体的单独对照实验中，给予低剂量多巴酚丁胺（2μg/kg/min）导致收缩周向应变率发生与 48 小时禁食期间相似的变化，同时 CSRd 成比例增加，使得这两个指标保持耦合。总之，这些数据表明，心肌脂肪变性通过损害健康成年人的舒张-收缩偶联导致舒张功能障碍，并表明脂肪变性可能导致心脏病的进展。要点：临床前证据强烈表明，心肌脂质积累（称为脂肪变性）是驱动心脏病的重要机制。由于多种潜在合并症的混杂影响，人类的明确证据有限。我们使用 48 小时禁食模型使年轻健康志愿者的心肌甘油三酯含量急性增加，证明了心肌脂肪变性与左心室舒张功能障碍之间存在关联。这些数据支持心肌脂肪变性可能导致舒张功能障碍的假设，并表明心肌脂肪变性作为潜在的治疗靶点。
