Circadian transcriptional pathway atlas highlights a proteasome switch in intermittent fasting.

Circadian transcriptional pathway atlas highlights a proteasome switch in intermittent fasting.
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昼夜节律转录途径图谱强调了间歇性禁食中的蛋白酶体开关

DOI:
10.1016/j.celrep.2022.111547
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发表时间:
2022-10-25
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影响因子:
8.8
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中科院分区:
生物学1区
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虽然间歇性禁食是一种有益健康的安全策略,但目前尚不清楚体内是否存在一个“计时器”来记录禁食时间并触发转录开关。在这里,我们绘制了一个昼夜转录途径图谱,从600个样本在四个代谢组织的小鼠在五个喂养方案。结果表明,95.6%的检测到的经典途径是有节奏的组织特异性和喂养方案特异性的方式,而只有不到25%的人诱导的转录功能的变化。禁食16小时启动了肝脏中43条通路的昼夜节律共振,并且该共振在重新进食后准时切换。肝脏蛋白酶体协调共振,大多数编码蛋白酶体亚基的基因显示16小时禁食依赖性转录开关。这些结果表明,肝蛋白酶体可能作为一个禁食定时器和协调器的途径转录共振,这为揭示间歇性禁食的潜在机制提供了一个目标。虽然间歇性禁食有益于健康,但每次禁食的最佳持续时间仍然是一个悬而未决的问题。Wei等人绘制了间歇性禁食的典型途径图谱,发现禁食16小时会引发肝脏中途径的昼夜节律共振,并将蛋白酶体确定为肝脏特异性禁食“计时器”。
While intermittent fasting is a safe strategy to benefit health, it remains unclear whether a “timer” exists in vivo to record fasting duration and trigger a transcriptional switch. Here, we map a circadian transcriptional pathway atlas from 600 samples across four metabolic tissues of mice under five feeding regimens. Results show that 95.6% of detected canonical pathways are rhythmic in a tissue-specific and feeding-regimen-specific manner, while only less than 25% of them induce changes in transcriptional function. Fasting for 16 h initiates a circadian resonance of 43 pathways in the liver, and the resonance punctually switches following refeeding. The hepatic proteasome coordinates the resonance, and most genes encoding proteasome subunits display a 16-h fasting-dependent transcriptional switch. These findings indicate that the hepatic proteasome may serve as a fasting timer and a coordinator of pathway transcriptional resonance, which provide a target for revealing the underlying mechanism of intermittent fasting. While intermittent fasting benefits health, the optimal duration of each fasting remains an open question. Wei et al. map an atlas of canonical pathways in intermittent fasting, find that fasting for 16 h initiates circadian resonance of pathways in the liver, and identify the proteasome as a liver-specific fasting “timer”.
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