Deciphering the decline of metabolic elasticity in aging and obesity.
Deciphering the decline of metabolic elasticity in aging and obesity.
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DOI：
10.1016/j.cmet.2023.08.001
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发表时间：
2023-08
期刊：
影响因子：
29
通讯作者：
Qiuzhong Zhou;Lexiang Yu;Joshua R. Cook;Li Qiang;Lei Sun
中科院分区：
文献类型：
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作者：
Qiuzhong Zhou;Lexiang Yu;Joshua R. Cook;Li Qiang;Lei Sun
生物体必须适应波动的养分供应，以维持能量平衡。在这里，我们术语的能力，这种适应和恢复的“代谢弹性”和模型，它alphoghad libitum-fasting-refeeding周期。代谢弹性是通过基因表达的协调多样性来实现的，我们称之为“基因弹性”。“我们已经开发了基因弹性评分作为一种系统的方法来量化小鼠和非人类灵长类动物代谢活性组织中转录组的弹性。参与脂质和碳水化合物代谢的基因显示出高基因弹性，并且它们的弹性随着年龄的增长而下降，特别是在脂肪组织中的PPARγ失调。通过喂食定时激动使PPARγ活性与营养条件同步优化其代谢益处和安全性。我们进一步扩大了代谢和基因弹性的概念范围，饮食的挑战，揭示了类似于那些在衰老的饮食引起的肥胖下降。总而言之，我们的研究结果为衰老和肥胖的代谢异常后果提供了一个动态的视角。
Organisms must adapt to fluctuating nutrient availability to maintain energy homeostasis. Here, we term the capacity for such adaptation and restoration "metabolic elasticity" and model it throughad libitum-fasting-refeeding cycles. Metabolic elasticity is achieved by coordinate versatility in gene expression, which we call "gene elasticity." We have developed the gene elasticity score as a systematic method to quantify the elasticity of the transcriptome across metabolically active tissues in mice and non-human primates. Genes involved in lipid and carbohydrate metabolism show high gene elasticity, and their elasticity declines with age, particularly with PPARγ dysregulation in adipose tissue. Synchronizing PPARγ activity with nutrient conditions through feeding-timed agonism optimizes their metabolic benefits and safety. We further broaden the conceptual scope of metabolic and gene elasticity to dietary challenges, revealing declines in diet-induced obesity similar to those in aging. Altogether, our findings provide a dynamic perspective on the dysmetabolic consequences of aging and obesity.