Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Translational Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
FASEB J. 2018 Jul;32(7):3844-3858. doi: 10.1096/fj.201701378RR. Epub 2018 Feb 27.
Evolutionary considerations suggest that the body has been optimized to perform at a high level in the food-deprived state when fatty acids and their ketone metabolites are a major fuel source for muscle cells. Because controlled food deprivation in laboratory animals and intermittent energy restriction in humans is a potent physiologic stimulus for ketosis, we designed a study to determine the impact of intermittent food deprivation during endurance training on performance and to elucidate the underlying cellular and molecular mechanisms. Male mice were randomly assigned to either ad libitum feeding or alternate-day food deprivation (ADF) groups, and half of the mice in each diet group were trained daily on a treadmill for 1 mo. A run to exhaustion endurance test performed at the end of the training period revealed superior performance in the mice maintained on ADF during training compared to mice fed ad libitum during training. Maximal O consumption was increased similarly by treadmill training in mice on ADF or ad libitum diets, whereas respiratory exchange ratio was reduced in ADF mice on food-deprivation days and during running. Analyses of gene expression in liver and soleus tissues, and metabolomics analysis of blood suggest that the metabolic switch invoked by ADF and potentiated by exercise strongly modulates molecular pathways involved in mitochondrial biogenesis, metabolism, and cellular plasticity. Our findings demonstrate that ADF engages metabolic and cellular signaling pathways that result in increased metabolic efficiency and endurance capacity.-Marosi, K., Moehl, K., Navas-Enamorado, I., Mitchell, S. J., Zhang, Y., Lehrmann, E., Aon, M. A., Cortassa, S., Becker, K. G., Mattson, M. P. Metabolic and molecular framework for the enhancement of endurance by intermittent food deprivation.
进化考虑表明，当脂肪酸及其酮体代谢物成为肌肉细胞的主要燃料来源时，身体已经优化到在禁食状态下高水平运作。由于实验室动物的控制禁食和人类的间歇性能量限制是酮症的有效生理刺激，我们设计了一项研究来确定在耐力训练期间间歇性禁食对表现的影响，并阐明潜在的细胞和分子机制。雄性小鼠被随机分配到自由进食或隔日禁食（ADF）组，每组一半的小鼠每天在跑步机上进行训练 1 个月。在训练期结束时进行的耗尽耐力测试表明，与在训练期间自由进食的小鼠相比，在训练期间接受 ADF 维持的小鼠表现更好。在 ADF 或自由进食饮食的小鼠中，跑步机训练同样增加了最大 O 消耗，而在禁食日和跑步时，ADF 小鼠的呼吸交换率降低。对肝脏和比目鱼肌组织的基因表达分析以及血液的代谢组学分析表明，ADF 引发的代谢转变和运动增强强烈调节了涉及线粒体生物发生、代谢和细胞可塑性的分子途径。我们的研究结果表明，ADF 参与了代谢和细胞信号通路，从而提高了代谢效率和耐力能力。-Marosi，K.，Moehl，K.，Navas-Enamorado，I.，Mitchell，S. J.，Zhang，Y.， Lehrmann，E.，Aon，M. A.，Cortassa，S.，Becker，K. G.，Mattson，M. P. 间歇性禁食增强耐力的代谢和分子框架。
