这种昼夜节律肝脏基因如何帮助人体在深夜和午夜吃零食后保持平稳的工作

这种昼夜节律肝脏基因如何帮助人体在深夜和午夜吃零食后保持平稳的工作
昼夜节律是我们健康的重要方面。
kanyanat wongsa / Shutterstock

Every living human is controlled by an internal “clock” which drives our circadian rhythm – the natural internal process that regulates our sleep-wake cycle during a 24-hour period.每个活着的人都受一个内部“时钟”控制,该时钟驱动我们的昼夜节律-调节XNUMX小时睡眠-觉醒周期的自然内部过程。 This internal clock controls most of our body processes over this period, including our sleep cycle, digestion, metabolism, appetite and immunity.这个内部时钟控制着我们这段时间的大部分身体过程,包括睡眠周期,消化,新陈代谢,食欲和免疫力。

External light levels, eating times and physical activity all act to keep the body clock synchronised to the external environment.外部光照水平,进食时间和体育锻炼都可以使体内时钟与外部环境保持同步。 Every cell in our body also has its own clock, which helps keep these processes working so seamlessly.人体中的每个细胞都有自己的时钟,这有助于使这些过程无缝地运行。 For example, clocks in individual tissues, such as the liver, work to ensure timely supply of energy to the rest of the body.例如,单个组织(例如肝脏)中的时钟可以确保向身体的其他部位及时提供能量。

But our circadian rhythm can be disrupted by any number of factors, including going to bed later than usual, or eating late at night.但是我们的昼夜节律可能会受到许多因素的干扰,包括比平时晚睡觉或深夜进食。 While occasional disruptions are no cause for alarm, research shows that long-term circadian rhythm disruption can cause poor health.尽管偶尔的干扰不会引起警报,但研究表明,长期的昼夜节律破坏会导致健康状况不佳。 For example, many studies have found that regular shift work increases the例如,许多研究发现,定期轮班会增加 肥胖的风险2型糖尿病。 And unfortunately,不幸的是, 昼夜节律紊乱 由于光污染,噪音和电子设备的出现,这在我们的社会中正变得越来越普遍,所有这些因素都可能加剧这些慢性健康状况。

But why is the body able to manage one-off instances of circadian rhythm disruption – such as staying up late on the weekend, or eating a late-night meal – without any health consequences?但是,为什么身体能够处理一次性的昼夜节律紊乱(例如,在周末熬夜或吃深夜饭)而没有任何健康后果呢? Our我们的 最近的工作 看看昼夜节律如何控制新陈代谢过程以匹配我们的日常食物摄取方式就可以解决问题。

肝基因“时钟”

One important component of our body clock is a protein called REVERBα.人体时钟的重要组成部分是一种称为REVERBα的蛋白质。 It is one of the network of proteins which keeps our body clock “ticking” in each organ of the body.它是蛋白质的网络之一,可以使我们的身体时钟在人体的每个器官中“滴答”。 However, natural genetic variation of the REVERBα gene is然而,REVERBα基因的自然遗传变异是 与肥胖有关 in humans.在人类中。 Research has also found that mice研究还发现,老鼠 缺乏基因 所有组织中的脂肪都会在器官内和器官周围积聚,如果进食高脂饮食,可能会变得非常肥胖。

We wanted to study more closely the action of REVERBα in the liver, as the liver is critical for maintaining energy balance, and its function is highly circadian, to cope with fasting during sleep.我们想更深入地研究REVERBα在肝脏中的作用,因为肝脏对于维持能量平衡至关重要,并且它的功能高度昼夜节律,可以应付睡眠中的禁食。 To do this, we used a new type of genetically modified mouse with the为此,我们使用了一种新型的转基因小鼠 REVERBα基因缺失 仅在肝脏中。

To our surprise, we discovered that deleting REVERBα has relatively little impact.令我们惊讶的是,我们发现删除REVERBα的影响相对较小。 In particular, we didn't see the accumulation of fat in the liver that we were expecting, and which is seen in animals which lack REVERBα in all tissues.特别是,我们没有看到我们期望的肝脏中脂肪的积聚,这在所有组织中都缺乏REVERBα的动物中也可以看到。 However, when we mapped liver genes that were likely to be under the control of REVERBα, we found thousands – including genes that are major regulators of energy and fat metabolism.但是,当我们绘制可能受REVERBα控制的肝脏基因的图谱时,我们发现了成千上万的基因,其中包括主要调节能量和脂肪代谢的基因。


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So we had a paradox: a circadian clock regulator with an extensive range of targets in the liver, yet it was not essential for normal liver function.因此,我们有一个悖论:昼夜​​节律调节器在肝脏中具有广泛的靶标,但对于正常的肝功能而言并不是必需的。 This raised two important issues.这就提出了两个重要的问题。 First, that under normal conditions REVERBα is ready, but not required to regulate fat metabolism.首先,在正常情况下,REVERBα已准备就绪,但不需要调节脂肪代谢。 And second, that the earlier findings linking REVERBα to obesity (and to the accumulation of fat in multiple organs) might actually arise from body-wide cues.第二,将REVERBα与肥胖症(以及脂肪在多个器官中的积累)联系起来的早期发现实际上可能来自于全身暗示。

Specifically, we thought that eating at unexpected times may be the cause for obesity.具体来说,我们认为在意外时间进食可能是肥胖的原因。 This is because mice lacking REVERBα throughout their body had an irregular eating pattern, especially feeding during their rest, or sleep period.这是因为整个体内缺乏REVERBα的小鼠的饮食习惯不规律,尤其是在休息或睡眠期间进食。

To test this idea, we analysed what happened when mice with REVERBα deleted in the liver were subjected to disrupted feeding schedules, rather like how shift work disrupts eating schedules.为了检验这个想法,我们分析了肝脏中缺失REVERBα的小鼠受到破坏的进食时间表,就像轮班工作如何破坏进食时间表一样。 Here, we discovered that disordered feeding caused a major change in the expression of genes that control fat metabolism – but only when REVERBα was deleted from the liver.在这里,我们发现饮食失调导致控制脂肪代谢的基因表达发生重大变化,但仅限于肝脏中REVERBα缺失的情况。 This suggests that REVERBα acts to smooth out the effects of disordered eating, as shown in our diagram below.这表明REVERBα可以消除饮食失调的影响,如下图所示。

REVERBα如何阻止昼夜节律“中断”

REVERBα如何阻止昼夜节律“中断”
丹妮尔·凯(Danielle Kay)
, 作者提供

In this way, all the internal clocks embedded in our body's tissues serve to protect against occasional changes in behaviour (such as the odd late-night meal).这样,嵌入在人体组织中的所有内部时钟都可以防止偶尔的行为变化(例如,奇怪的深夜进餐)。 However, when we are constantly doing things that go against our natural circadian rhythm – such as always eating late, or working night shifts – this protective system is overwhelmed, leading to obesity and diabetes.但是,当我们不断做一些与我们的自然昼夜节律背道而驰的事情时(例如,总是吃晚或上夜班),这种保护系统就会不堪重负,导致肥胖和糖尿病。

Our study therefore highlights the importance of eating meals in sync with the body clock, during the day.因此,我们的研究强调了在白天与人体时钟同步进餐的重要性。 To keep our liver clock ticking – and to keep our whole circadian rhythm working properly – it's important to develop an eating schedule that has a clear separation between the fed period (typically during the day), and the fasted period (typically during the night).为了使我们的肝脏时钟保持节拍,并保持整个昼夜节律正常运行,重要的是制定饮食计划,使进食期(通常在白天)和禁食期(通常在晚上)之间有明显的区别。 This is hard for shift workers, depending on shift schedule, so strategies to help are urgently needed.对于轮班工人来说,这很困难,具体取决于轮班时间表,因此迫切需要帮助的策略。谈话

作者简介

内分泌学教授David Ray 牛津大学; David Bechtold, Professor of Physiology,生理学教授David Bechtold, 英国曼彻斯特大学以及内分泌学和糖尿病讲师Louise Hunter, 英国曼彻斯特大学

本文重新发表 谈话 根据知识共享许可。 阅读 原创文章.


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