Link between obesity and sleep loss

肥胖和失眠之间的关联

上海译锐翻译  2020-4-30   15:38 p.m.

Can staying up late make you fat? A growing body of research has suggested that poor sleep quality is linked to an increased risk of obesity by deregulating appetite, which in turn leads to more calorie consumption.

晚睡会让人变胖吗？越来越多的研究表明，糟糕的睡眠与不断增加的肥胖风险有关。糟糕的睡眠会让食欲失控，而这反过来会导致摄入更多的卡路里。

But a new study published this week in PLOS Biology found that the direction of this reaction might actually be flipped: It's not the sleep loss that leads to obesity, but rather that excess weight can cause poor sleep, according to researchers from the University of Pennsylvania's Perelman School of Medicine and the University of Nevada, Reno, who discovered their findings in the microscopic worm Caenorhabditis elegans (C. elegans).

然而，本周在《公共科学图书馆生物学》（PLoS Biology）发表的一项新研究论文发现，这一反应的方向可能实际被颠倒了：并非失眠导致肥胖，而是肥胖会导致糟糕的睡眠。来自宾夕法尼亚大学佩雷尔曼医学院（Perelman School of Medicine）及内华达大学里诺校区的研究者们在一种叫做秀丽线虫（C. elegans）的微生物蠕虫中获得了这一发现。

"We think that sleep is a function of the body trying to conserve energy in a setting where energetic levels are going down. Our findings suggest that if you were to fast for a day, we would predict you might get sleepy because your energetic stores would be depleted," said study co-author David Raizen, MD, PhD, an associate professor of Neurology and member of the Chronobiology and Sleep Institute at Penn.

“我们认为，睡眠是身体在能量水平下降情况下试图保存能量的一种功能。我们的研究发现，如果你打算禁食一天，那么我们可以预见，你可能会犯困，这是因为你的能量储备可能会被耗尽，”论文共同作者David Raizen，医学博士、博士、神经学副教授及宾夕法尼亚大学时间生物学和睡眠研究所成员表示。

Raizen emphasized that while these findings in worms may not translate directly to humans, C. elegans offer a surprisingly good model for studying mammalian slumber. Like all other animals that have nervous systems, they need sleep. But unlike humans, who have complex neural circuitry and are difficult to study, a C. elegans has only 302 neurons -- one of which scientists know for certain is a sleep regulator.

Raizen强调表示，尽管有关蠕虫的研究结果可能不会直接应用到人类身上，但是秀丽线虫却为我们研究哺乳动物的睡眠提供了一种非常理想的模型。和所有其他拥有神经系统的动物一样，这种蠕虫需要睡眠。人类具有复杂的神经元回路且研究起来非常有难度。与人类不同，秀丽线虫只有302个神经元，而科学家们确信，这其中之一就是睡眠调节器。

In humans, acute sleep disruption can result in increased appetite and insulin resistance, and people who chronically get fewer than six hours of sleep per night are more likely be obese and diabetic. Moreover, starvation in humans, rats, fruit flies, and worms has been shown to affect sleep, indicating that it is regulated, at least in part, by nutrient availability. However, the ways in which sleeping and eating work in tandem has remained unclear.

在人类当中，突然的睡眠中断会导致食欲增加和胰岛素阻抗性升高。而长期每晚睡眠不足6小时的人群则更可能肥胖并患有糖尿病。此外，当人类、老鼠、果蝇和蠕虫处于饥饿状态时，已表明睡眠会受到影响，这说明，睡眠至少在一定程度上受养分可利用性调节。然而，睡眠和饮食共同作用的方式则仍然属于未解之谜。

"We wanted to know, what is sleep actually doing? Short sleep and other chronic conditions, like diabetes, are linked, but it's just an association. It's not clear if short sleep is causing the propensity for obesity, or that the obesity, perhaps, causes the propensity for short sleep," said study co-author Alexander van der Linden, PhD, an associate professor of Biology at the University of Nevada, Reno.

“我们想要知道，睡眠到底在发挥什么作用？睡眠时间短和其他慢性疾病，如糖尿病之间存在关联，但这只是一种联系。我们现在还不清楚是睡眠时间短容易导致肥胖，还是肥胖导致睡眠时间短，”论文的共同作者Alexander van der Linden，博士，内华达大学里诺校区生物学副教授表示。

To study the association between metabolism and sleep, the researchers genetically modified C. elegans to "turn off" a neuron that controls sleep. These worms could still eat, breathe, and reproduce, but they lost their ability to sleep. With this neuron turned off, the researchers saw a severe drop in adenosine triphosphate (ATP) levels, which is the body's energy currency.

为了研究新陈代谢和睡眠之间的关联，研究人员修改了秀丽线虫的基因，并将控制睡眠的神经元“关闭”。神经元被关闭的蠕虫仍旧会进食，会呼吸，会繁殖，但是它们失去了睡觉的能力。随着这一神经元的关闭，研究人员发现激活腺苷三磷酸（ATP）水平急剧下降，而这属于身体的能量通货。

"That suggests that sleep is an attempt to conserve energy; it's not actually causing the loss of energy," Raizen explained.

“这表明睡眠试图保存能量；实际上，睡眠并不会引起能量消耗，”Raizen解释道。

In previous research, the van der Linden lab studied a gene in C. elegans called KIN-29. This gene is homologous to the Salt-Inducible Kinase (SIK-3) gene in humans, which was already known to signal sleep pressure. Surprisingly, when the researchers knocked out the KIN-29 gene to create sleepless worms, the mutant C. elegans accumulated excess fat -- resembling the human obesity condition -- even though their ATP levels lowered.

在之前的研究中，van der Linden实验室对秀丽线虫中一种叫做KIN-29的基因展开研究。这个基因与人类中的盐诱导激酶（SIK-3）类似。SIK-3能够预示睡眠压力的作用已为人们所知。令人惊讶的是，当研究人员关闭KIN-29基因并打造出一种不睡眠的蠕虫后，即使是在ATP水平下降的前提下，变异后的蠕虫仍堆积了多余脂肪，这与人类的肥胖情况很相似。

The researchers hypothesized that the release of fat stores is a mechanism for which sleep is promoted, and that the reason KIN-29 mutants did not sleep is because they were unable to liberate their fat. To test this hypothesis, the researchers again manipulated the KIN-29 mutant worms, this time expressing an enzyme that "freed" their fat. With that manipulation, the worms were again able to sleep.

研究人员假设，所存脂肪的释放是一个促进睡眠的机制，而这也是KIN-29变异蠕虫睡觉的原因，这是因为它们无法释放脂肪。为了验证这一假设，研究人员再次改变KIN-29变异蠕虫，这次表现出一种可以释放脂肪的酶。通过改变后，蠕虫能够再次入睡。

Raizen said this could explain one reason why people with obesity may experience sleep problems. "There could be a signaling problem between the fat stores and the brain cells that control sleep," he said.

Raizen表示，这可能解释了为什么肥胖人群可能会遇到睡眠问题。他认为，“脂肪储备与大脑细胞之间可能存在一种神秘信号，这种信号可以控制睡眠。”

While there is still much to unravel about sleep, Raizen said that this paper takes the research community one step closer to understanding one of its core functions -- and how to treat common sleep disorders.

尽管关于睡眠还有诸多谜团待解，但是Raizen认为，这篇文章可以让研究人员更进一步了解睡眠的核心功能之一以及如何治疗常见的睡眠障碍。

"There is a common, over-arching sentiment in the sleep field that sleep is all about the brain, or the nerve cells, and our work suggests that this isn't necessarily true," he said. "There is some complex interaction between the brain and the rest of the body that connects to sleep regulation."

“在睡眠界有一种非常普遍和广泛的理解，那就是睡眠完全和大脑或神经细胞有关。而我们的研究则表明，这一观点未必是正确的。大脑和身体其余部分之间存在一些复杂的互动，而这些互动与睡眠的调节有关联。”

来源：科学日报    编辑：上海译锐翻译质控部Susan