Brewer Rachel A, Collins Helen E, Berry Ryan D, Brahma Manoja K, Tirado Brian A, Peliciari-Garcia Rodrigo A, Stanley Haley L, Wende Adam R, Taegtmeyer Heinrich, Rajasekaran Namakkal Soorappan, Darley-Usmar Victor, Zhang Jianhua, Frank Stuart J, Chatham John C, Young Martin E
Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Division of Molecular Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Life Sci. 2018 Mar 15;197:30-39. doi: 10.1016/j.lfs.2018.01.031. Epub 2018 Feb 1.
Recent studies suggest that the time of day at which food is consumed dramatically influences clinically-relevant cardiometabolic parameters (e.g., adiposity, insulin sensitivity, and cardiac function). Meal feeding benefits may be the result of daily periods of feeding and/or fasting, highlighting the need for improved understanding of the temporal adaptation of cardiometabolic tissues (e.g., heart) to fasting. Such studies may provide mechanistic insight regarding how time-of-day-dependent feeding/fasting cycles influence cardiac function. We hypothesized that fasting during the sleep period elicits beneficial adaptation of the heart at transcriptional, translational, and metabolic levels. To test this hypothesis, temporal adaptation was investigated in wild-type mice fasted for 24-h, or for either the 12-h light/sleep phase or the 12-h dark/awake phase. Fasting maximally induced fatty acid responsive genes (e.g., Pdk4) during the dark/active phase; transcriptional changes were mirrored at translational (e.g., PDK4) and metabolic flux (e.g., glucose/oleate oxidation) levels. Similarly, maximal repression of myocardial p-mTOR and protein synthesis rates occurred during the dark phase; both parameters remained elevated in the heart of fasted mice during the light phase. In contrast, markers of autophagy (e.g., LC3II) exhibited peak responses to fasting during the light phase. Collectively, these data show that responsiveness of the heart to fasting is temporally partitioned. Autophagy peaks during the light/sleep phase, while repression of glucose utilization and protein synthesis is maximized during the dark/active phase. We speculate that sleep phase fasting may benefit cardiac function through augmentation of protein/cellular constituent turnover.
最近的研究表明，进食的时间对临床相关的心脏代谢参数（如肥胖、胰岛素敏感性和心脏功能）有显著影响。进食的益处可能是由于每日的进食和/或禁食周期，这突出了更好地理解心脏代谢组织（如心脏）对禁食的时间适应性的必要性。此类研究可能会提供关于昼夜依赖性进食/禁食周期如何影响心脏功能的机制性见解。我们假设，在睡眠期间禁食会在转录、翻译和代谢水平上引发心脏的有益适应性变化。为了验证这一假设，我们研究了野生型小鼠在禁食24小时、或在12小时光照/睡眠阶段或12小时黑暗/清醒阶段的时间适应性。禁食在黑暗/活跃阶段最大程度地诱导了脂肪酸反应基因（如Pdk4）；转录变化在翻译（如PDK4）和代谢通量（如葡萄糖/油酸氧化）水平上得到反映。同样，心肌p-mTOR和蛋白质合成速率的最大抑制发生在黑暗阶段；在禁食小鼠的心脏中，这两个参数在光照阶段仍保持升高。相比之下，自噬标志物（如LC3II）在光照阶段对禁食表现出峰值反应。总体而言，这些数据表明心脏对禁食的反应在时间上是有区分的。自噬在光照/睡眠阶段达到峰值，而葡萄糖利用和蛋白质合成的抑制在黑暗/活跃阶段达到最大。我们推测，睡眠阶段禁食可能通过增强蛋白质/细胞成分更新而有益于心脏功能。
