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Imagine the typical office birthday party.
It's after lunch, so everybody is full. Then, in comes a luscious chocolate confection. The sight, the smell -- even the sound of the word 'cake!' -- stimulate the reward-and-pleasure circuits of the brain, activating memory centers and salivary glands as well.
Those reactions quickly drown out the subtle signals from the stomach that are saying, in effect, 'Still digesting down here. Don't send more!' Social cues add pressure and permission to indulge. Soon, everybody is having a slice -- or two.
Scholars have understood the different motives for eating as far back as Socrates, who counseled, 'Thou shouldst eat to live, not live to eat.' But nowadays, scientists are using sophisticated brain-imaging technology to understand how the lure of delicious food can overwhelm the body's built-in mechanism to regulate hunger and fullness, what's called 'hedonic' versus 'homeostatic' eating.
One thing is clear: Obese people react much more hedonistically to sweet, fat-laden food in the pleasure and reward circuits of the brain than healthy-weight people do. Simply seeing pictures of tempting food can light up the pleasure-seeking areas of obese peoples' brains.
Two conferences this week on obesity are each examining aspects of how appetite works in the brain and why some people ignore their built-in fullness signals. Scientists hope that breakthroughs will lead to ways to retrain people's thinking about food or weight-loss drugs that can target certain brain areas.
In a study presented this week at the International Conference on Obesity in Stockholm, researchers from Columbia University in New York showed pictures of cake, pies, french fries and other high-calorie foods to 10 obese women and 10 non-obese women and monitored their brain reactions on fMRI scans. In the obese women, the images triggered a strong response in the ventral tegmental area (VTA), a tiny spot in the midbrain where dopamine, the 'desire chemical,' is released. The images also activated the ventral pallidum, a part of the brain involved in planning to do something rewarding.
'When obese people see high-calorie foods, a widespread network of brain areas involved in reward, attention, emotion, memory and motor planning is activated, and all the areas talk to each other, making it hard for them to resist,' says lead investigator Susan Carnell, a research psychiatrist at the New York Obesity Research Center at Columbia University.
Similar brain reactions occurred in the obese subjects even when researchers merely said the words 'chocolate brownie' -- but not when they saw or heard about lower calorie foods such as cabbage and zucchini. Reactions were far less pronounced in the non-obese subjects.
More such studies are being presented in Pittsburgh this week at the annual meeting of the Society for the Study of Ingestive Behavior. In one, neuroscientists from Yale University's John B. Pierce Laboratory had 13 overweight and 13 normal-weight subjects smell and taste chocolate or strawberry milkshakes and observed their brains with fMRI scans.
The overweight subjects had strong reactions to the food in the amygdala -- the emotional center of the brain -- whether they were hungry or not. The healthy-weight subjects showed an amygdala response only when they were hungry.
'If you are of normal weight, your homeostatic mechanisms are functioning and controlling this region of the brain,' says lead investigator Dana Small. 'But in the overweight group, there is some sort of dysfunction in the homeostatic signal so that even though they weren't hungry, they were vulnerable to these external eating cues.'
Studies have found that a diet of sweet, high-fat foods can indeed blunt the body's built-in fullness signals. Most of them emanate from the digestive tract, which releases chemical messengers including cholecystokinin, glucagon-like peptide and peptide YY when the stomach and intestines are full. Those signals travel up to the brain stem and then the hypothalamus, telling the body to stop eating.
Obesity also throws off the action of leptin, a hormone secreted by fat tissue that tells the hypothalamus how much energy the body has stored. Leptin should act as a brake against overeating, and it does in normal-weight people. But most obese people have an overabundance of leptin, and somehow their brains are ignoring the signal.
All these findings beg the question, which came first? Does obesity disrupt the action of leptin, or does a malfunction in leptin signaling make people obese?
Similarly, are some people obese because their brains overreact to tempting food, or do their brains react that way because something else is driving them to overeat? Researchers at Yale and elsewhere are turning to such questions next. 'It's possible that these changes reflect how the brain has adapted to eating patterns in obese people, and that could create a vicious circle, putting them at risk for even more disordered eating.' says Dr. Small.
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让我们来想象一场典型的同事们给某人过生日的派对场面。
中饭吃完了，大家都吃得很饱。然后，服务员送进来一个美味的巧克力蛋糕。蛋糕的形状和香味──甚至是“蛋糕”这个词本身──都激起人们脑部的快感满足回路(pleasure and reward circuit)，对蛋糕美味的记忆随之开启，唾腺开始分泌。
此时，人们的胃部正发出微弱的信号：“这里还在消化，别再吃了。”然而，对蛋糕的自然反应很快占据压倒性优势。集体的心理暗示让每个人都觉得吃蛋糕是一种理所当然的快乐之事。很快，大家就开始分而食之，一块，或是两块。
学者们早就知道，人类的进食存在各种各样的动机，希腊哲学家苏格拉底(Socrates)有一句劝诫的名言：“你应该为了活而吃，而不是为了吃而活。”('Thou shouldst eat to live, not live to eat.')但现在，科学家正借助先进的脑部成像技术来探查，为何美食的诱惑能够战胜体内控制饥饿和饱腹感的生理机制，也就是“为了快乐而吃”和“为了需求而吃”到底孰强孰弱。
有一点很清楚：肥胖人群在面对高糖分高脂肪的食品时，脑部快感体验回路的反应要比体重正常的人群积极得多。只要看到美食的图片，肥胖人群脑部寻求快感的区域就马上活跃起来。
2010年7月中旬举办的两场肥胖问题研讨会都在研究人体脑部的食欲反应机制，以及为什么有些人会忽视体内的饱腹感信号。科学家希望在该领域的突破将有助于改变人们对食物的渴求程度，或研究出能影响脑部特定区域的减肥药。
其中一个会议是在斯德哥尔摩举办的肥胖问题国际研讨会(International Conference on Obesity)。在会上，来自纽约州哥伦比亚大学(Columbia University)的研究人员向10名超重女性和10名非超重女性展示了蛋糕、馅饼、薯条等高热量食品的图片，并通过功能磁共振成像(fMRI)扫描仪观察她们的脑部反应。超重女性的中脑腹侧被盖区(ventral tegmental, VTA)迅速产生强烈的反应，导致中脑一个微小的区域分泌出被称为“欲望化学物质”的多巴胺(dopamine)。这些图片也激活了她们的腹侧苍白球(ventral pallidum, VP)，一个跟快感体验行为相关的脑部区域。
“肥胖人群看到高热量食品时，涉及快感体验、关注、情绪、记忆和动作计划的一系列脑部区域开始启动，各个脑部区域相互沟通，导致他们很难抗拒进食的诱惑。”哥伦比亚大学纽约肥胖研究中心(New York Obesity Research Center)的首席研究员苏珊.卡奈尔(Susan Carnell)说道。
即使研究人员只是开口说“黑森林蛋糕”，接受观察的肥胖者脑部也会产生同样的反应，但当他们看到或听到卷心菜和西葫芦等低热量食品时，脑部对此无动于衷。对于非肥胖人群来说，这种反差则要小得多。
摄食行为研究学会(Society for the Study of Ingestive Behavior)的年会本周在匹兹堡举行，有更多的研究成果在会上公布出来。举例而言，耶鲁大学(Yale University)约翰•皮尔斯实验室(John B. Pierce Laboratory)神经学家们让13名超重者和13名正常体重者用鼻子闻并品尝巧克力奶昔或者草莓奶昔，通过功能磁共振成像扫描仪观察他们的脑部活动。
超重者的脑部杏仁核区域（大脑的情绪中心）对食物产生强烈反应──无论他们是否感到饥饿。体重正常者则只有在饥饿的时候杏仁核区才会有类似反应。
“如果你体重正常，那说明你体内的自平衡机制在发挥作用，正控制着脑部的这块区域。” 约翰•皮尔斯实验室首席研究员斯莫尔(Dana Small)说，“但对超重者来说，他们的自平衡机制有点问题，因此即使不饿，也抵抗不了外界的美食诱惑。”
研究还发现，高糖分高脂肪的食品确实会让人体内的饱腹信号变得迟钝起来。绝大多数这类信号来自于消化道，当胃部和肠道装满食物时，会释放出一些化学信使来传递饱腹信号，包括胆囊收缩素、胰高血糖素样肽和肽YY。这些信号依次传输到脑干和丘脑下部，指示身体停止进食。
肥胖人群受瘦素(leptin)的影响也不明显。瘦素是一种由脂肪组织分泌的激素，能告诉丘脑下部体内已经储存了多少能量，还能制止人体过多进食。正常体重者体内的瘦素在发挥作用，但大多数肥胖者瘦素分泌过剩，导致其脑部忽略了瘦素传递出的信息。
所有这些研究都指向一个问题：谁才是罪魁祸首？是肥胖扰乱了瘦素的作用，还是瘦素信号失常导致人们变得肥胖？
还有与此类似的一个问题，是一些人的脑部对美食做出过激反应造成其身体变胖，还是有别的因素驱使他们过多进食从而导致脑部作出过激反应？耶鲁大学和其他机构的研究人员下一步就要研究这些问题。“是否存在这种可能性，即肥胖人群对美食的过激反应表明其脑部已经适应了不良的饮食习惯，从而形成恶性循环，导致肥胖者出现更严重的进食紊乱。”斯莫尔说道。
