EGCG ameliorates diet-induced metabolic syndrome associating with the circadian clock
EGCG ameliorates diet-induced metabolic syndrome associating with the circadian clock
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EGCG 可改善饮食诱发的与生物钟相关的代谢综合征
DOI：
10.1016/j.bbadis.2017.04.009
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发表时间：
2017-06-01
影响因子：
6.2
通讯作者：
Liu, Xuebo
中科院分区：
文献类型：
--
作者：
Mi, Yashi;Qi, Guoyuan;Liu, Xuebo
为了响应每日的光-暗（LD）循环，地球上的生物已经进化出大约24小时的内源性振荡，以协调行为和生理过程，包括进食，睡眠和代谢稳态。由富含脂肪和果糖的高能量饮食引发的昼夜节律紊乱与一系列代谢紊乱密切相关。以往的研究表明，（-）-表没食子儿茶素-3-没食子酸酯（EGCG）可以减轻代谢失调;然而，只有少数报告集中在其直接操纵昼夜节律，以改善代谢综合征的潜在影响。我们的目标是研究EGCG治疗对高脂高果糖饮食（HFFD）引发的与昼夜节律钟相关的代谢失调的调节作用。我们的研究结果表明，HFFD治疗部分表现出较差的昼夜节律振荡的核心时钟基因和时钟控制的基因在肝脏和脂肪相对于对照组。通过控制Sirt 1-PGC 1 α环，给予EGCG可以改善昼夜节律功能的饮食依赖性下降，这意味着存在一个EGCG可抑制的振荡器。随后，在小鼠的EGCG组中观察到的肝脏中脂肪酸合成减少和β-氧化升高以及棕色脂肪组织（BAT）能量消耗增加阻止了脂肪细胞肥大和脂肪积累，这是源自HFFD小鼠的BAT和白色脂肪组织（WAT）所共有的。这项研究首次提供了令人信服的证据，表明EGCG可以通过调节肝脏和脂肪中生物钟基因的节律表达来改善饮食诱导的代谢失调。
In response to the daily light-dark (LD) cycle, organisms on Earth have evolved with the approximately 24-h endogenous oscillations to coordinate behavioral and physiological processes, including feeding, sleep, and metabolism homeostasis. Circadian desynchrony triggered by an energy-dense diet rich in fats and fructose is intimately connected with a series of metabolic disorders. Previous studies revealed that (-)-Epigallocatechin-3-gallate (EGCG) could mitigate metabolic misalignment; however, only a few reports have focused on its potential effect on directly manipulating circadian rhythms to ameliorate metabolic syndrome. Our goal was to investigate the regulating effect of EGCG treatment on metabolic misalignment triggered by a high-fat and high-fructose diet (HFFD) associating with the circadian clock. Our results indicated that HFFD treatment partially exhibited poor circadian oscillations of the core clock gene and the clock-controlled gene in the liver and fat relative to the control group. EGCG administration may ameliorate the diet-dependent decline in circadian function by controlling the Sirt1-PGC1 alpha loop, implying the existence of an EGCG-entrainable oscillator. Subsequently, reducing fatty acid synthesis and elevating beta-oxidation in the liver coupled with the increasing brown adipose tissue (BAT) energy expenditure observed in the EGCG group of mice prevented the adipocyte hypertrophy and fat accumulations common to BAT and white adipose tissue (WAT) derived from the HFFD mice. This study is the first to provide compelling evidences that EGCG may ameliorate diet-induced metabolic misalignment by regulating the rhythmic expression of the circadian clock genes in the liver and fat.