Obesity¹ may have harmful effects on the brain, and exercise may counteract² 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 precisely³ the same way to fat and physical activity, the findings offer one more reason to get out and exercise.

科学家们最近在小鼠身上进行了一项复杂的新型神经生物学实验，其结果显示，肥胖会对大脑造成有害影响，而运动可以抵消上述负面影响中的绝大部分，即使在动物的体重并未大幅减轻时也一样有效。虽然我们不可能知道人类大脑是否会以完全相同的方式来应答脂肪和体育活动，但起码这些研究结果为我们走出户外进行运动又提供了一条新的理由。

It's been known for some time that obesity can alter cognition in animals. Past experiments with lab rodents⁴, for instance, have shown that obese⁵ 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 mazes⁶ that they've negotiated multiple times.

一段时间之前，人们已经发现肥胖可以改变动物的认知。例如，关于实验室啮齿类动物的既往实验表明，肥胖动物的记忆力和学习能力均低于体重正常的同类动物。它们无法辨认出熟悉的物体，而且哪怕已经多次从迷宫中走过，它们仍然记不住出口的位置。

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，科学家们一直没有弄明白体重超重是如何影响大脑的。据他们所知，脂肪细胞可以制造出某些物质并将其释放入血液。这些物质随着血流来到身体的其他部位，包括心脏和肌肉等，然后在那里迅速启动一系列的生化过程，造成严重的炎症和其他疾病，导致健康状况恶化。

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 undesirable⁷ molecules⁸.

不过人们一直以为大脑应该可以从上述有害影响中幸免于难。因为大脑本身并不包含脂肪细胞，且它安居于血-脑屏障的保护之后，这道屏障通常足以将危险分子阻挡于大脑之外。

However, recent disquieting⁹ studies in animals indicate that obesity weakens that barrier, leaving it leaky and permeable. In obese animals, substances released by fat cells can ooze¹⁰ past the barrier and into the brain.

然而，近期的动物研究结果却十分令人不安。这些研究表明，肥胖可削弱血-脑屏障，使它变得具有泄漏性和渗透性。在肥胖动物中，脂肪细胞释放的物质可以突破血-脑屏障，进入大脑。

The consequences of that seepage¹¹ 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 accomplished¹². 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.

乔治亚瑞金斯大学（Georgia Regents University，位于美国奥古斯塔）的研究人员以这种渗漏造成的后果为对象进行了一系列新颖的神经生物学实验，并将其发表于上个月的《神经科学杂志》(The Journal of Neuroscience)上。出于研究需要，科学家们首先搜集了一些容易过食和肥胖的小鼠。这些小鼠可以好几周都安静地坐在笼子里，随心所欲地吃啊吃。等它们长得圆嘟嘟的，并积累了较多的脂肪细胞后，它们差不多就合格了。研究人员对它们进行了检查，并发现在它们的血液中有一种名为白细胞介素1(interleukin 1)的物质浓度日益增加，这种物质由脂肪细胞产生，且目前已知它会引起炎症。

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 essentially¹³ 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.

当白细胞介素1随着血液来到这些小鼠的头部后，就穿过血脑屏障进入了海马（与学习和记忆有关的关键部位）等脑区，并把这些组织的正常工作搞得一团糟。在检查过这些动物的大脑组织后，研究人员发现其中存在着高水平的白细胞介素1，炎症标志物也有广泛分布。虽说炎症是身体对入侵分子的一种健康反应，但它如果持续不断，就会对细胞造成伤害。

The researchers also noted¹⁴ extremely low levels in these mice brains of a biochemical associated with healthy synapse¹⁵ function. Synapses¹⁶ 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' inflamed¹⁷ brains, synapses were no longer functioning properly and messages between neurons likely jerked, hiccuped¹⁸ or stalled.

研究人员还指出，在这些小鼠的大脑中，与健康的突触功能相关的生化标志物水平非常低。突触是指连接一个神经元与另一个神经元，并在它们之间传递信息的结构。健康的突触可应大脑的要求做出相应的反应，减慢或加快信息的传递，从而保持大脑的神经系统交通始终处于井然有序的管理之下。肥胖动物发炎的大脑中突触健康的标志物水平偏低，这提示研究人员它们脑中突触的运作已经失常，神经元间的信息传递也不再顺畅，甚至有可能出现停滞。

That possibility was borne out by subsequent tests on the memory and thinking of some of the remaining obese mice. They performed miserably¹⁹.

这种可能性很快就在后续的实验中得到了证实：研究人员对其余的肥胖小鼠进行了记忆和思维测试，它们的表现惨不忍睹。

But whether excessive fat cells alone were the underlying²⁰ cause of the changes in the animals' brains was not clear. Other physiological²¹ factors "could have been contributing," said Alexis Stranahan, a professor at the Medical College of Georgia at Georgia Regents, who oversaw²² the study. So, to isolate²³ the impact of the fat, the researchers simply removed most of it, surgically²⁴ excising²⁵ the large bands of fat that each mouse bore around its middle.

只是，人们一时还无法确定促使这些动物的大脑发生改变的根本原因是否仅限于脂肪细胞过剩。其他的生理因素“也可能发挥了一定作用，”该研究的负责人、乔治亚瑞金斯大学乔治亚医学院(Medical College of Georgia)的教授亚历克西斯·斯特拉纳汉(Alexis Stranahan)说。因此，为了将脂肪的影响单独分离出来，研究人员在每只小鼠的身体中段打了个孔，通过手术切除了大块大块的脂肪——可以说是它们体内的绝大部分脂肪。

After recovery, these slenderized mice showed almost no interleukin 1 in their bloodstreams and, Algernon-like, soon were acing²⁶ cognitive²⁷ tests that had stumped²⁸ them before surgery.

等这些接受了抽脂瘦身的小鼠痊愈后，它们血液中的白细胞介素1全都几乎不见了，就像科幻小说里面的阿尔杰农（Algernon，是科幻小说《献给阿尔杰农的花》中一只接受脑部改造手术实验的仓鼠——译注）一样，它们不费吹灰之力就搞定了手术前一直把它们难倒的认知测试。

Conversely, when the scientists implanted the preserved fat pads into previously²⁹ 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，当科学家们将之前保存下来的脂肪垫植入到以前纤瘦的小鼠体内（我们谁不曾做过这样的噩梦，梦见就在我们呼呼大睡时类似的厄运降临到我们自己身上？）时，它们几乎是立即就变得呆呆傻傻的，在认知测试中的表现也比过去糟糕许多，尽管它们生活中其他的各个方面都一如往常。

The results convincingly implicated³⁰ fat cells as the primary cause of the mice's cognitive decline.

这些研究结果令人信服地证明了脂肪细胞即是造成小鼠认知能力下降的元凶。

But while provocative³¹, 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 excised³² from the obese mice.

只是虽然这些发现弄得人心痒难耐，科学家们却认识到它对人类而言几乎没有什么实用价值，因为即便是人体所能承受的最广泛的吸脂手术，它所清除的脂肪量也要远远少于实验中从肥胖小鼠体内清除的脂肪量。

So the scientists turned, as a less-invasive alternative, to exercise. Gathering³³ 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 treadmill³⁴ running, with encouragement provided by small puffs³⁵ of air if they began to flag. The other mice remained sedentary.

因此，科学家们将目光转向了无创性的替代方案：运动。他们收集了更多具有肥胖倾向的小鼠，并让它们都长到肥胖超重的程度。然后，他们将这些小鼠分作两半，让其中一半每天在小鼠跑步机上跑步45分钟，并在它们显出疲态时为它们吹送小小的“顺风”来鼓励它们。其余的小鼠则仍保持其久坐不动的生活方式。

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 robust³⁶ 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，每天跑步的小鼠体重依旧与从未运动的小鼠差不多。但他们身体中段的脂肪量已经显著减少，肌肉量却不断增加。更有说服力的是，它们在认知测试中的成绩远远优于久坐不动的小鼠。此外，在研究人员检查它们的海马组织时，也几乎没有看到任何可表明炎症存在的证据，反之，表征突触健康的化学标志物则十分充足。正如科学家们在研究论文中所写的，这些研究结果表明，“跑步机训练使海马的功能变得正常”，即使在那些天生容易发胖且仍然体重超重的动物中依然如此。

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 tantalizing³⁷, 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.

当然，这些研究都是在小鼠中进行的，人类的大脑很可能以迥异的方式来作应答。但我们也无法排除这一诱人的可能性：说不定人类大脑会与之类似呢？斯特拉纳汉博士指出，她这项研究的结论非常值得借鉴。“走出门去做运动吧，”她说，如果你腰上已经带了个“救生圈”就尤其需要赶快行动。跟你的医生谈谈，制定一个安全、可以承受的锻炼计划，然后尝试照着它坚持下去，让超重的体重不再那么让你伤脑筋。