Fasting and time of day independently modulate circadian rhythm relevant gene expression in adipose and skin tissue.

Fasting and time of day independently modulate circadian rhythm relevant gene expression in adipose and skin tissue.
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DOI:
10.1186/s12864-018-4997-y
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发表时间:
2018-09-07
期刊:
影响因子:
4.4
通讯作者:
Small KS
Small KS
中科院分区:
生物学2区
文献类型:
--
作者:
Couto Alves A;Glastonbury CA;El-Sayed Moustafa JS;Small KS

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间歇性禁食和限时饮食与心脏代谢疾病的低风险生物标志物相关。对这些事件的相似生理反应的共同机制尚未确定,但可能涉及昼夜节律。在这里,我们对健康志愿者(N = 625)的脂肪和皮肤组织进行了一项大型横断面研究,研究了对禁食的转录反应,控制了昼夜节律的混杂因素:一天中的时间和季节。我们在脂肪中鉴定出367个基因,在皮肤中鉴定出79个基因,它们的表达水平与禁食时间相关(FDR < 5%),与一天中的时间和季节无关,其中19个基因在两种组织中都是共同的。在这些基因中,我们在人类研究中复制了38个,在非人类研究中复制了157个,178个是新的关联。富含对昼夜节律进行调控和响应的禁食反应基因。我们在脂肪中发现了99个基因,在皮肤中发现了54个基因,它们的表达与一天中的时间有关;这些基因也丰富了昼夜节律过程。在与两种暴露相关的基因中,一天中时间的影响更强,而且与禁食时间的影响方向相反。我们还研究了禁食与基因表达的遗传调控之间的关系,包括GxE eQTL分析,以确定个人对禁食的反应。这项研究有力地暗示了昼夜节律基因对禁食时间的反应与一天中的时间、季节性、年龄和体重指数无关。我们在大量健康志愿者样本中确定了禁食转录反应的组织共享和组织特异性差异。本文的在线版本(10.1186/s12864-018-4997-y)包含补充材料,授权用户可以使用。
Intermittent fasting and time-restricted diets are associated with lower risk biomarkers for cardio-metabolic disease. The shared mechanisms underpinning the similar physiological response to these events is not established, but circadian rhythm could be involved. Here we investigated the transcriptional response to fasting in a large cross-sectional study of adipose and skin tissue from healthy volunteers (N = 625) controlling for confounders of circadian rhythm: time of day and season. We identified 367 genes in adipose and 79 in skin whose expression levels were associated (FDR < 5%) with hours of fasting conditionally independent of time of day and season, with 19 genes common to both tissues. Among these genes, we replicated 38 in human, 157 in non-human studies, and 178 are novel associations. Fasting-responsive genes were enriched for regulation of and response to circadian rhythm. We identified 99 genes in adipose and 54 genes in skin whose expression was associated to time of day; these genes were also enriched for circadian rhythm processes. In genes associated to both exposures the effect of time of day was stronger and in an opposite direction to that of hours fasted. We also investigated the relationship between fasting and genetic regulation of gene expression, including GxE eQTL analysis to identify personal responses to fasting. This study robustly implicates circadian rhythm genes in the response to hours fasting independently of time of day, seasonality, age and BMI. We identified tissue-shared and tissue-specific differences in the transcriptional response to fasting in a large sample of healthy volunteers. The online version of this article (10.1186/s12864-018-4997-y) contains supplementary material, which is available to authorized users.
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