Lack of food intake during shift work alters the heart transcriptome and leads to cardiac tissue fibrosis and inflammation in rats.

Lack of food intake during shift work alters the heart transcriptome and leads to cardiac tissue fibrosis and inflammation in rats.
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DOI:
10.1186/s12915-022-01256-9
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发表时间:
2022-03-03
期刊:
影响因子:
5.4
通讯作者:
Menet JS
Menet JS
中科院分区:
生物学2区
文献类型:
--
作者:
Trott AJ;Greenwell BJ;Karhadkar TR;Guerrero-Vargas NN;Escobar C;Buijs RM;Menet JS

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许多流行病学研究表明,轮班工作与包括心血管疾病在内的一些疾病的风险增加有关。大鼠轮班工作的实验模型还被证明可以概括在人类轮班工人中观察到的代谢紊乱的各个方面,包括脂肪含量增加和葡萄糖耐量受损,并用于证明限制工作时间外的食物消费可以预防轮班工作相关的肥胖和代谢紊乱。然而,不同的轮班工作参数,如工作类型,数量和持续时间,影响心血管功能和潜在的机制,仍然知之甚少。在这里,我们使用大鼠作为模型来表征轮班工作对心脏的影响,并确定它们是否可以通过在正常活动期限制食物摄入来调节。我们表明,实验轮班工作重新编程的心脏循环转录组独立的食物消耗。虽然在对照组大鼠中,节律基因表达的阶段分布在24小时内,但在轮班工人中,它们聚集在离散的时间内。此外,在轮班工作期间防止食物摄入会影响心脏中数百个基因的表达水平,包括编码细胞外基质组分的基因和在与压力超负荷和心脏肥大相关的转录特征中发现的炎症标记物。与此一致,轮班工人大鼠的心脏在工作时间内不进食,但在轮班工作之外可以获得食物,表现出增加的胶原蛋白1沉积,并表现出增加的免疫细胞浸润。虽然在轮班工作期间保持食物获取对基因表达的影响较小,但在心脏肥大的转录特征中发现的基因仍然受到影响,轮班工作大鼠的心脏表现出纤维化而没有炎症。总之,我们的研究结果揭示了食物消耗对轮班工作大鼠心脏重塑转录谱的差异影响。他们还提供了关于轮班工作如何影响心脏功能的见解,并建议一些旨在减轻轮班工人代谢紊乱的干预措施可能对心血管疾病产生不利影响。在线版本包含补充材料,可通过10.1186/s12915-022-01256-9获得。
Many epidemiological studies revealed that shift work is associated with an increased risk of a number of pathologies, including cardiovascular diseases. An experimental model of shift work in rats has additionally been shown to recapitulate aspects of metabolic disorders observed in human shift workers, including increased fat content and impaired glucose tolerance, and used to demonstrate that restricting food consumption outside working hours prevents shift work-associated obesity and metabolic disturbance. However, the way distinct shift work parameters, such as type of work, quantity, and duration, affect cardiovascular function and the underlying mechanisms, remains poorly understood. Here, we used the rat as a model to characterize the effects of shift work in the heart and determine whether they can be modulated by restricting food intake during the normal active phase. We show that experimental shift work reprograms the heart cycling transcriptome independently of food consumption. While phases of rhythmic gene expression are distributed across the 24-h day in control rats, they are clustered towards discrete times in shift workers. Additionally, preventing food intake during shift work affects the expression level of hundreds of genes in the heart, including genes encoding components of the extracellular matrix and inflammatory markers found in transcriptional signatures associated with pressure overload and cardiac hypertrophy. Consistent with this, the heart of shift worker rats not eating during work hours, but having access to food outside of shift work, exhibits increased collagen 1 deposition and displays increased infiltration by immune cells. While maintaining food access during shift work has less effects on gene expression, genes found in transcriptional signatures of cardiac hypertrophy remain affected, and the heart of shift worker rats exhibits fibrosis without inflammation. Together, our findings unraveled differential effects of food consumption on remodeled transcriptional profiles of the heart in shift worker rats. They also provide insights into how shift work affects cardiac function and suggest that some interventions aiming at mitigating metabolic disorders in shift workers may have adverse effects on cardiovascular diseases. The online version contains supplementary material available at 10.1186/s12915-022-01256-9.
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