雙語(yǔ)：肥胖有損大腦 運(yùn)動(dòng)修復(fù)智力

Obesity may have harmful effects on the brain, and exercise may counteract many of those negative effects, according to sophisticated new neurological experiments with mice, even when the animals do not lose much weight. While it's impossible to know if human brains respond in precisely the same way to fat and physical activity, the findings offer one more reason to get out and exercise.

科學(xué)家們最近在小鼠身上進(jìn)行了一項(xiàng)復(fù)雜的新型神經(jīng)生物學(xué)實(shí)驗(yàn)，其結(jié)果顯示，肥胖會(huì)對(duì)大腦造成有害影響，而運(yùn)動(dòng)可以抵消上述負(fù)面影響中的絕大部分，即使在動(dòng)物的體重并未大幅減輕時(shí)也一樣有效。雖然我們不可能知道人類(lèi)大腦是否會(huì)以完全相同的方式來(lái)應(yīng)答脂肪和體育活動(dòng)，但起碼這些研究結(jié)果為我們走出戶外進(jìn)行運(yùn)動(dòng)又提供了一條新的理由。

It's been known for some time that obesity can alter cognition in animals. Past experiments with lab rodents, for instance, have shown that obese animals display poor memory and learning skills compared to their normal-weight peers. They don't recognize familiar objects or recall the location of the exit in mazes that they've negotiated multiple times.

一段時(shí)間之前，人們已經(jīng)發(fā)現(xiàn)肥胖可以改變動(dòng)物的認(rèn)知。例如，關(guān)于實(shí)驗(yàn)室嚙齒類(lèi)動(dòng)物的既往實(shí)驗(yàn)表明，肥胖動(dòng)物的記憶力和學(xué)習(xí)能力均低于體重正常的同類(lèi)動(dòng)物。它們無(wú)法辨認(rèn)出熟悉的物體，而且哪怕已經(jīng)多次從迷宮中走過(guò)，它們?nèi)匀挥洸蛔〕隹诘奈恢谩?/span>

But scientists hadn't understood how excess weight affects the brain. Fat cells, they knew, manufacture and release substances into the bloodstream that flow to other parts of the body, including the heart and muscles. There, these substances jump-start biochemical processes that produce severe inflammation and other conditions that can lead to poor health.

但是，科學(xué)家們一直沒(méi)有弄明白體重超重是如何影響大腦的。據(jù)他們所知，脂肪細(xì)胞可以制造出某些物質(zhì)并將其釋放入血液。這些物質(zhì)隨著血流來(lái)到身體的其他部位，包括心臟和肌肉等，然后在那里迅速啟動(dòng)一系列的生化過(guò)程，造成嚴(yán)重的炎癥和其他疾病，導(dǎo)致健康狀況惡化。

Many thought the brain, though, should be insulated from those harmful effects. It contains no fat cells and sits behind the protective blood-brain barrier that usually blocks the entry of undesirable molecules.

不過(guò)人們一直以為大腦應(yīng)該可以從上述有害影響中幸免于難。因?yàn)榇竽X本身并不包含脂肪細(xì)胞，且它安居于血-腦屏障的保護(hù)之后，這道屏障通常足以將危險(xiǎn)分子阻擋于大腦之外。

However, recent disquieting studies in animals indicate that obesity weakens that barrier, leaving it leaky and permeable. In obese animals, substances released by fat cells can ooze past the barrier and into the brain.

然而，近期的動(dòng)物研究結(jié)果卻十分令人不安。這些研究表明，肥胖可削弱血-腦屏障，使它變得具有泄漏性和滲透性。在肥胖動(dòng)物中，脂肪細(xì)胞釋放的物質(zhì)可以突破血-腦屏障，進(jìn)入大腦。

The consequences of that seepage became the subject of new neurological experiments conducted by researchers at Georgia Regents University in Augusta and published last month in The Journal of Neuroscience.

For the studies, the scientists gathered mice bred to overeat and grow obese, which, after a few weeks of sitting quietly in their cages and eating at will, the animals had obligingly accomplished. As they grew rotund and accumulated more fat cells, the researchers found, their blood showed increasingly hefty doses of a substance called interleukin 1 that is created by fat cells and known to cause inflammation.

喬治亞瑞金斯大學(xué)（Georgia Regents University，位于美國(guó)奧古斯塔）的研究人員以這種滲漏造成的后果為對(duì)象進(jìn)行了一系列新穎的神經(jīng)生物學(xué)實(shí)驗(yàn)，并將其發(fā)表于上個(gè)月的《神經(jīng)科學(xué)雜志》(The Journal of Neuroscience)上。

出于研究需要，科學(xué)家們首先搜集了一些容易過(guò)食和肥胖的小鼠。這些小鼠可以好幾周都安靜地坐在籠子里，隨心所欲地吃啊吃。等它們長(zhǎng)得圓嘟嘟的，并積累了較多的脂肪細(xì)胞后，它們差不多就合格了。研究人員對(duì)它們進(jìn)行了檢查，并發(fā)現(xiàn)在它們的血液中有一種名為白細(xì)胞介素1(interleukin 1)的物質(zhì)濃度日益增加，這種物質(zhì)由脂肪細(xì)胞產(chǎn)生，且目前已知它會(huì)引起炎癥。

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In these mice, as interleukin 1 migrated to the head, it passed the blood-brain barrier and entered areas such as the hippocampus, a part of the brain critical for learning and memory. There, it essentially gummed up the works, the researchers found when they examined tissue from the animals' brains, which had high levels of interleukin 1 together with widespread markers of inflammation. While inflammation can represent a healthy response to invading molecules, it hurts cells if it persists.

當(dāng)白細(xì)胞介素1隨著血液來(lái)到這些小鼠的頭部后，就穿過(guò)血腦屏障進(jìn)入了海馬（與學(xué)習(xí)和記憶有關(guān)的關(guān)鍵部位）等腦區(qū)，并把這些組織的正常工作搞得一團(tuán)糟。在檢查過(guò)這些動(dòng)物的大腦組織后，研究人員發(fā)現(xiàn)其中存在著高水平的白細(xì)胞介素1，炎癥標(biāo)志物也有廣泛分布。雖說(shuō)炎癥是身體對(duì)入侵分子的一種健康反應(yīng)，但它如果持續(xù)不斷，就會(huì)對(duì)細(xì)胞造成傷害。

The researchers also noted extremely low levels in these mice brains of a biochemical associated with healthy synapse function. Synapses are the structures that connect one neuron to another and shunt messages between them. Healthy synapses respond to demands on the brain by slowing or speeding messages, keeping the brain's nervous-system traffic manageable.

But low levels of the marker of synapse health suggested to the researchers that in these obese animals' inflamed brains, synapses were no longer functioning properly and messages between neurons likely jerked, hiccuped or stalled.

研究人員還指出，在這些小鼠的大腦中，與健康的突觸功能相關(guān)的生化標(biāo)志物水平非常低。突觸是指連接一個(gè)神經(jīng)元與另一個(gè)神經(jīng)元，并在它們之間傳遞信息的結(jié)構(gòu)。健康的突觸可應(yīng)大腦的要求做出相應(yīng)的反應(yīng)，減慢或加快信息的傳遞，從而保持大腦的神經(jīng)系統(tǒng)交通始終處于井然有序的管理之下。

肥胖動(dòng)物發(fā)炎的大腦中突觸健康的標(biāo)志物水平偏低，這提示研究人員它們腦中突觸的運(yùn)作已經(jīng)失常，神經(jīng)元間的信息傳遞也不再順暢，甚至有可能出現(xiàn)停滯。

That possibility was borne out by subsequent tests on the memory and thinking of some of the remaining obese mice. They performed miserably.

這種可能性很快就在后續(xù)的實(shí)驗(yàn)中得到了證實(shí)：研究人員對(duì)其余的肥胖小鼠進(jìn)行了記憶和思維測(cè)試，它們的表現(xiàn)慘不忍睹。

But whether excessive fat cells alone were the underlying cause of the changes in the animals' brains was not clear. Other physiological factors "could have been contributing," said Alexis Stranahan, a professor at the Medical College of Georgia at Georgia Regents, who oversaw the study.

So, to isolate the impact of the fat, the researchers simply removed most of it, surgically excising the large bands of fat that each mouse bore around its middle.

只是，人們一時(shí)還無(wú)法確定促使這些動(dòng)物的大腦發(fā)生改變的根本原因是否僅限于脂肪細(xì)胞過(guò)剩。其他的生理因素“也可能發(fā)揮了一定作用，”該研究的負(fù)責(zé)人、喬治亞瑞金斯大學(xué)喬治亞醫(yī)學(xué)院(Medical College of Georgia)的教授亞歷克西斯·斯特拉納漢(Alexis Stranahan)說(shuō)。

因此，為了將脂肪的影響單獨(dú)分離出來(lái)，研究人員在每只小鼠的身體中段打了個(gè)孔，通過(guò)手術(shù)切除了大塊大塊的脂肪——可以說(shuō)是它們體內(nèi)的絕大部分脂肪。

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After recovery, these slenderized mice showed almost no interleukin 1 in their bloodstreams and, Algernon-like, soon were acing cognitive tests that had stumped them before surgery.

等這些接受了抽脂瘦身的小鼠痊愈后，它們血液中的白細(xì)胞介素1全都幾乎不見(jiàn)了，就像科幻小說(shuō)里面的阿爾杰農(nóng)（Algernon，是科幻小說(shuō)《獻(xiàn)給阿爾杰農(nóng)的花》中一只接受腦部改造手術(shù)實(shí)驗(yàn)的倉(cāng)鼠——譯注）一樣，它們不費(fèi)吹灰之力就搞定了手術(shù)前一直把它們難倒的認(rèn)知測(cè)試。

Conversely, when the scientists implanted the preserved fat pads into previously lean mice — and haven't we all had nightmares about something like that happening to us in our sleep? — the animals almost immediately grew dimmer, performing far worse than previously on cognitive tests, although nothing else in their lives had changed.

反之，當(dāng)科學(xué)家們將之前保存下來(lái)的脂肪墊植入到以前纖瘦的小鼠體內(nèi)（我們誰(shuí)不曾做過(guò)這樣的噩夢(mèng)，夢(mèng)見(jiàn)就在我們呼呼大睡時(shí)類(lèi)似的厄運(yùn)降臨到我們自己身上？）時(shí)，它們幾乎是立即就變得呆呆傻傻的，在認(rèn)知測(cè)試中的表現(xiàn)也比過(guò)去糟糕許多，盡管它們生活中其他的各個(gè)方面都一如往常。

The results convincingly implicated fat cells as the primary cause of the mice's cognitive decline.

這些研究結(jié)果令人信服地證明了脂肪細(xì)胞即是造成小鼠認(rèn)知能力下降的元兇。

But while provocative, the findings had little practical value for people, the scientists realized, since even the most extensive liposuction procedure in humans would remove far less fat than had been excised from the obese mice.

只是雖然這些發(fā)現(xiàn)弄得人心癢難耐，科學(xué)家們卻認(rèn)識(shí)到它對(duì)人類(lèi)而言幾乎沒(méi)有什么實(shí)用價(jià)值，因?yàn)榧幢闶侨梭w所能承受的最廣泛的吸脂手術(shù)，它所清除的脂肪量也要遠(yuǎn)遠(yuǎn)少于實(shí)驗(yàn)中從肥胖小鼠體內(nèi)清除的脂肪量。

So the scientists turned, as a less-invasive alternative, to exercise. Gathering more of the obesity-prone mice, they allowed all of them to grow heavy, but then started half on a daily 45-minute program of treadmill running, with encouragement provided by small puffs of air if they began to flag. The other mice remained sedentary.

因此，科學(xué)家們將目光轉(zhuǎn)向了無(wú)創(chuàng)性的替代方案：運(yùn)動(dòng)。他們收集了更多具有肥胖傾向的小鼠，并讓它們都長(zhǎng)到肥胖超重的程度。然后，他們將這些小鼠分作兩半，讓其中一半每天在小鼠跑步機(jī)上跑步45分鐘，并在它們顯出疲態(tài)時(shí)為它們吹送小小的“順風(fēng)”來(lái)鼓勵(lì)它們。其余的小鼠則仍保持其久坐不動(dòng)的生活方式。

After 12 weeks, the running mice still weighed about the same as the unexercised animals. But they had lost significant amounts of fat from around their middles, while adding lean muscle. More telling, they did much better on cognitive tests than the sedentary mice and, when the researchers examined tissue from their hippocampi, showed little evidence of inflammation and robust levels of the chemical marker of synaptic health. The results suggested that, as the scientists write in the study, "treadmill training normalized hippocampal function," even in animals born to be fat and that remained heavy.

12周后，每天跑步的小鼠體重依舊與從未運(yùn)動(dòng)的小鼠差不多。但他們身體中段的脂肪量已經(jīng)顯著減少，肌肉量卻不斷增加。更有說(shuō)服力的是，它們?cè)谡J(rèn)知測(cè)試中的成績(jī)遠(yuǎn)遠(yuǎn)優(yōu)于久坐不動(dòng)的小鼠。此外，在研究人員檢查它們的海馬組織時(shí)，也幾乎沒(méi)有看到任何可表明炎癥存在的證據(jù)，反之，表征突觸健康的化學(xué)標(biāo)志物則十分充足。正如科學(xué)家們?cè)谘芯空撐闹兴鶎?xiě)的，這些研究結(jié)果表明，“跑步機(jī)訓(xùn)練使海馬的功能變得正常”，即使在那些天生容易發(fā)胖且仍然體重超重的動(dòng)物中依然如此。

Of course, these studies were conducted in mice, not people, whose brains may respond very differently. But the possibility that humans, too, may respond in similar ways is tantalizing, Dr. Stranahan said, and the takeaway from her study worth repeating. "Get out and move," she said, even — and especially — if you carry extra weight. Talk with your doctor about a safe and tolerable exercise program, and then try to stick with that routine so that extra pounds won't weigh too heavily on your mind.

當(dāng)然，這些研究都是在小鼠中進(jìn)行的，人類(lèi)的大腦很可能以迥異的方式來(lái)作應(yīng)答。但我們也無(wú)法排除這一誘人的可能性：說(shuō)不定人類(lèi)大腦會(huì)與之類(lèi)似呢？斯特拉納漢博士指出，她這項(xiàng)研究的結(jié)論非常值得借鑒。“走出門(mén)去做運(yùn)動(dòng)吧，”她說(shuō)，如果你腰上已經(jīng)帶了個(gè)“救生圈”就尤其需要趕快行動(dòng)。跟你的醫(yī)生談?wù)劊�制定一個(gè)安全、可以承受的鍛煉計(jì)劃，然后嘗試照著它堅(jiān)持下去，讓超重的體重不再那么讓你傷腦筋。

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