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Link between obesity and sleep loss

肥胖和失眠之間的關(guān)聯(lián)

上海譯銳翻譯  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.

晚睡會讓人變胖嗎？越來越多的研究表明，糟糕的睡眠與不斷增加的肥胖風(fēng)險有關(guān)。糟糕的睡眠會讓食欲失控，而這反過來會導(dǎo)致攝入更多的卡路里。

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《公共科學(xué)圖書館生物學(xué)》（PLoS Biology）發(fā)表的一項新研究論文發(fā)現(xiàn)，這一反應(yīng)的方向可能實際被顛倒了：并非失眠導(dǎo)致肥胖，而是肥胖會導(dǎo)致糟糕的睡眠。來自賓夕法尼亞大學(xué)佩雷爾曼醫(yī)學(xué)院（Perelman School of Medicine）及內(nèi)華達大學(xué)里諾校區(qū)的研究者們在一種叫做秀麗線蟲（C. elegans）的微生物蠕蟲中獲得了這一發(fā)現(xiàn)。

"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.

“我們認(rèn)為，睡眠是身體在能量水平下降情況下試圖保存能量的一種功能。我們的研究發(fā)現(xiàn)，如果你打算禁食一天，那么我們可以預(yù)見，你可能會犯困，這是因為你的能量儲備可能會被耗盡，”論文共同作者David Raizen，醫(yī)學(xué)博士、博士、神經(jīng)學(xué)副教授及賓夕法尼亞大學(xué)時間生物學(xué)和睡眠研究所成員表示。

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強調(diào)表示，盡管有關(guān)蠕蟲的研究結(jié)果可能不會直接應(yīng)用到人類身上，但是秀麗線蟲卻為我們研究哺乳動物的睡眠提供了一種非常理想的模型。和所有其他擁有神經(jīng)系統(tǒng)的動物一樣，這種蠕蟲需要睡眠。人類具有復(fù)雜的神經(jīng)元回路且研究起來非常有難度。與人類不同，秀麗線蟲只有302個神經(jīng)元，而科學(xué)家們確信，這其中之一就是睡眠調(diào)節(jié)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.

在人類當(dāng)中，突然的睡眠中斷會導(dǎo)致食欲增加和胰島素阻抗性升高。而長期每晚睡眠不足6小時的人群則更可能肥胖并患有糖尿病。此外，當(dāng)人類、老鼠、果蠅和蠕蟲處于饑餓狀態(tài)時，已表明睡眠會受到影響，這說明，睡眠至少在一定程度上受養(yǎng)分可利用性調(diào)節(jié)。然而，睡眠和飲食共同作用的方式則仍然屬于未解之謎。

"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.

“我們想要知道，睡眠到底在發(fā)揮什么作用？睡眠時間短和其他慢性疾病，如糖尿病之間存在關(guān)聯(lián)，但這只是一種聯(lián)系。我們現(xiàn)在還不清楚是睡眠時間短容易導(dǎo)致肥胖，還是肥胖導(dǎo)致睡眠時間短，”論文的共同作者Alexander van der Linden，博士，內(nèi)華達大學(xué)里諾校區(qū)生物學(xué)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.

為了研究新陳代謝和睡眠之間的關(guān)聯(lián)，研究人員修改了秀麗線蟲的基因，并將控制睡眠的神經(jīng)元“關(guān)閉”。神經(jīng)元被關(guān)閉的蠕蟲仍舊會進食，會呼吸，會繁殖，但是它們失去了睡覺的能力。隨著這一神經(jīng)元的關(guān)閉，研究人員發(fā)現(xiàn)激活腺苷三磷酸（ATP）水平急劇下降，而這屬于身體的能量通貨。

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

“這表明睡眠試圖保存能量；實際上，睡眠并不會引起能量消耗，”Raizen解釋道。

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實驗室對秀麗線蟲中一種叫做KIN-29的基因展開研究。這個基因與人類中的鹽誘導(dǎo)激酶（SIK-3）類似。SIK-3能夠預(yù)示睡眠壓力的作用已為人們所知。令人驚訝的是，當(dāng)研究人員關(guān)閉KIN-29基因并打造出一種不睡眠的蠕蟲后，即使是在ATP水平下降的前提下，變異后的蠕蟲仍堆積了多余脂肪，這與人類的肥胖情況很相似。

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.

研究人員假設(shè)，所存脂肪的釋放是一個促進睡眠的機制，而這也是KIN-29變異蠕蟲睡覺的原因，這是因為它們無法釋放脂肪。為了驗證這一假設(shè)，研究人員再次改變KIN-29變異蠕蟲，這次表現(xiàn)出一種可以釋放脂肪的酶。通過改變后，蠕蟲能夠再次入睡。

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，這可能解釋了為什么肥胖人群可能會遇到睡眠問題。他認(rèn)為，“脂肪儲備與大腦細(xì)胞之間可能存在一種神秘信號，這種信號可以控制睡眠。”

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.

盡管關(guān)于睡眠還有諸多謎團待解，但是Raizen認(rèn)為，這篇文章可以讓研究人員更進一步了解睡眠的核心功能之一以及如何治療常見的睡眠障礙。

"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."

“在睡眠界有一種非常普遍和廣泛的理解，那就是睡眠完全和大腦或神經(jīng)細(xì)胞有關(guān)。而我們的研究則表明，這一觀點未必是正確的。大腦和身體其余部分之間存在一些復(fù)雜的互動，而這些互動與睡眠的調(diào)節(jié)有關(guān)聯(lián)。”

來源：科學(xué)日報    編輯：上海譯銳翻譯質(zhì)控部Susan