肥胖有損大腦,運動修復智力大綱

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.

科學家們最近在小鼠身上進行了一項複雜的新型神經生物學實驗，其結果顯示，肥胖會對大腦造成有害影響，而運動可以抵消上述負面影響中的絕大部分，即使在動物的體重並未大幅減輕時也一樣有效。雖然我們不可能知道人類大腦是否會以完全相同的方式來應答脂肪和體育活動，但起碼這些研究結果爲我們走出戶外進行運動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.

一段時間之前，人們已經發現肥胖可以改變動物的認知。例如，關於實驗室齧齒類動物的既往實驗表明，肥胖動物的記憶力和學習能力均低於體重正常的同類動物。它們無法辨認出熟悉的物體，而且哪怕已經多次從迷宮中走過，它們仍然記不住出口的位置。

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，科學家們一直沒有弄明白體重超重是如何影響大腦的。據他們所知，脂肪細胞可以製造出某些物質並將其釋放入血液。這些物質隨着血流來到身體的其他部位，包括心臟和肌肉等，然後在那裏迅速啓動一系列的生化過程，造成嚴重的炎症和其他疾病，導致健康狀況惡化。

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.

不過人們一直以爲大腦應該可以從上述有害影響中倖免於難。因爲大腦本身並不包含脂肪細胞，且它安居於血-腦屏障的保護之後，這道屏障通常足以將危險分子阻擋於大腦之外。

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，近期的動物研究結果卻十分令人不安。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。在肥胖動物中，脂肪細胞釋放的物質可以突破血-腦屏障，進入大腦。

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（Georgia Regents University，位於美國奧古斯塔）的研究人員以這種滲漏造成的後果爲對象進行了一系列新穎的神經生物學實驗，並將其發表於上個月的《神經科學雜誌》(The Journal of Neuroscience)上。出於研究需要，科學家們首先蒐集了一些容易過食和肥胖的小鼠。這些小鼠可以好幾周都安靜地坐在籠子裏，隨心所欲地吃啊吃。等它們長得圓嘟嘟的，並積累了較多的脂肪細胞後，它們差不多就合格了。研究人員對它們進行了檢查，並發現在它們的血液中有一種名爲白細胞介素1(interleukin 1)的物質濃度日益增加，這種物質由脂肪細胞產生，且目前已知它會引起炎症。

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.

當白細胞介素1隨着血液來到這些小鼠的頭部後，就穿過血腦屏障進入了海馬（與學習和記憶有關的關鍵部位）等腦區，並把這些組織的正常工作搞得一團糟。在檢查過這些動物的大腦組織後，研究人員發現其中存在着高水平的白細胞介素1，炎症標誌物也有廣泛分佈。雖說炎症是身體對入侵分子的一種健康反應，但它如果持續不斷，就會對細胞造成傷害。

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的生化標誌物水平非常低。突觸是指連接一個神經元與另一個神經元，並在它們之間傳遞信息的結構。健康的突觸可應大腦的要求做出相應的反應，減慢或加快信息的傳遞，從而保持大腦的神經系統交通始終處於井然有序的管理之下。肥胖動物發炎的大腦中突觸健康的標誌物水平偏低，這提示研究人員它們腦中突觸的運作已經失常，神經元間的信息傳遞也不再順暢，甚至有可能出現停滯。

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後續的實驗中得到了證實：研究人員對其餘的肥胖小鼠進行了記憶和思維測試，它們的表現慘不忍睹。

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，人們一時還無法確定促使這些動物的大腦發生改變的根本原因是否僅限於脂肪細胞過剩。其他的生理因素“也可能發揮了一定作用，”該研究的負責人、喬治亞瑞金斯大學喬治亞醫學院(Medical College of Georgia)的教授亞歷克西斯·斯特拉納漢(Alexis Stranahan)說。因此，爲了將脂肪的影響單獨分離出來，研究人員在每隻小鼠的身體中段打了個孔，通過手術切除了大塊大塊的脂肪——可以說是它們體內的絕大部分脂肪。

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癒後，它們血液中的白細胞介素1全都幾乎不見了，就像科幻小說裏面的阿爾傑農（Algernon，是科幻小說《獻給阿爾傑農的花》中一隻接受腦部改造手術實驗的倉鼠——譯註）一樣，它們不費吹灰之力就搞定了手術前一直把它們難倒的認知測試。

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，當科學家們將之前保存下來的脂肪墊植入到以前纖瘦的小鼠體內（我們誰不曾做過這樣的噩夢，夢見就在我們呼呼大睡時類似的厄運降臨到我們自己身上？）時，它們幾乎是立即就變得呆呆傻傻的，在認知測試中的表現也比過去糟糕許多，儘管它們生活中其他的各個方面都一如往常。

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

這些研究結果令人信服地證明了脂肪細胞即是造成小鼠認知能力下降的元兇。

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.

只是雖然這些發現弄得人心癢難耐，科學家們卻認識到它對人類而言幾乎沒有什麼實用價值，因爲即便是人體所能承受的最廣泛的吸脂手術，它所清除的脂肪量也要遠遠少於實驗中從肥胖小鼠體內清除的脂肪量。

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，科學家們將目光轉向了無創性的替代方案：運動。他們收集了更多具有肥胖傾向的小鼠，並讓它們都長到肥胖超重的程度。然後，他們將這些小鼠分作兩半，讓其中一半每天在小鼠跑步機上跑步45分鐘，並在它們顯出疲態時爲它們吹送小小的“順風”來鼓勵它們。其餘的小鼠則仍保持其久坐不動的生活方式。

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周後，每天跑步的小鼠體重依舊與從未運動的小鼠差不多。但他們身體中段的脂肪量已經顯著減少，肌肉量卻不斷增加。更有說服力的是，它們在認知測試中的成績遠遠優於久坐不動的小鼠。此外，在研究人員檢查它們的海馬組織時，也幾乎沒有看到任何可表明炎症存在的證據，反之，表徵突觸健康的化學標誌物則十分充足。正如科學家們在研究論文中所寫的，這些研究結果表明，“跑步機訓練使海馬的功能變得正常”，即使在那些天生容易發胖且仍然體重超重的動物中依然如此。

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.

當然，這些研究都是在小鼠中進行的，人類的大腦很可能以迥異的方式來作應答。但我們也無法排除這一誘人的可能性：說不定人類大腦會與之類似呢？斯特拉納漢博士指出，她這項研究的結論非常值得借鑑。“走出門去做運動吧，”她說，如果你腰上已經帶了個“救生圈”就尤其需要趕快行動。跟你的醫生談談，制定一個安全、可以承受的鍛鍊計劃，然後嘗試照着它堅持下去，讓超重的體重不再那麼讓你傷腦筋。