SO, YOU ATE less and exercised more and managed to lose weight. But now what you lost is piling back on. You're hungrier than ever and you can't seem to resist food. Once again, it's all your fault, right?
Wrong. Blame evolution, and the fact that for the vast majority of human history, famine was a bigger threat than flab. Even your seeming lack of will power is tied up in the complex biological systems that drive humans who have lost weight to regain it, according to new brain-scan research by scientists at Columbia University Medical Center.
'Loosely put, after you've lost weight, you have more of an emotional response to food and less ability to control that response,' says Michael Rosenbaum, lead author of the study in this month's Journal of Clinical Investigation.
The key driver of this system is leptin, a hormone secreted by fat cells. When humans (and rodents) lose 10% or more of their body weight, leptin falls rapidly and sets off a cascade of physiological changes that act to put weight back on. Skeletal muscles work more efficiently, thyroid and other hormones are reduced -- all so the body burns 15% to 20% fewer calories.
'If you have two people of the same weight, but one lost 10% of his body weight to reach that point, that person will either need to burn 300 to 400 calories more per day, or eat 300 to 400 calories less to stay at that weight,' says Dr. Rosenbaum. That's enough to put back more than 11 kilograms a year.
This mechanism kicks in whether people are obese or relatively lean before they lose weight -- and researchers believe the effect can last for years. However, in previous studies, when subjects were given replacement leptin, the metabolic changes were reversed and they were able to maintain their weight loss. In effect, their bodies were tricked into overlooking the fact that it had lost weight.
The latest study shows that the metabolic changes resulting from weight loss are mirrored in altered brain activity. The Columbia researchers carefully controlled the intake of six hospitalized obese patients using liquid diets. Their weight was reduced by 10% and they were given either replacement leptin or a placebo. At each stage, researchers observed their brain activity using functional MRIs when they were shown food and nonfood items.
The scans showed that in the weight-reduced state, the subjects had more blood flow in areas of the brain related to emotional and sensory responses to food and less in areas involving control of food intake. When they were given replacement leptin, those changes were reversed and brain activity returned to what it had been before they lost weight.
There are still many unknowns about how blood flow in the brain corresponds to behavior. 'I can't look at these scans and say, in 30 seconds, you're going to eat a banana,' says Rudolph Leibel, a co-author of the Columbia study who helped discover leptin in the 1990s at Rockefeller University. Still, he says, it is further evidence of the powerful biological one-two punch that leptin delivers to people who have lost weight: 'These people act as if they were hungrier and combined with reduced energy expenditure, that's the 'perfect storm' for gaining weight.'
Researchers originally thought leptin signaled the body to stop eating and hoped that it might be harnessed as a weight-loss drug. Instead, leptin's role is to prevent weight loss, and a drop in leptin levels sends the body into survival mode when food is scarce and fat stores decline. That makes sense from an evolutionary standpoint, but helps fuel obesity in modern times. For most of human history, 'you had to spend a lot of energy to get food,' says Dr. Leibel. Now, 'anyone can summon an unlimited amount of food just with a cellphone.'
Scientists think that leptin may still have a role as a drug for maintaining weight loss, which they now see as a different mechanism than losing weight in the first place. Amylin Pharmaceuticals Inc. of San Diego, which bought the rights to leptin from Amgen Inc. in 2006, is testing it, in combination with pramlintide, a diabetes drug. Large-scale human trials won't start until next year at the earliest.
In the meantime, how do some people manage to overcome the biological imperatives? Generally by watching their food intake very carefully and continuing to increase their physical activity. 'Anybody who has lost weight and kept it off will tell you that they have to keep battling,' says Dr. Rosenbaum. 'They have essentially reinvented themselves, and they are worthy of the utmost admiration and respect.'
错。现在你可以将其怪罪于人类的进化。回顾人类历史，绝大部分时间，饥饿对人造成的威胁都要超过肥胖。表面上看，你是缺乏意志力才导致减肥后体重反弹；但根据哥伦比亚大学医学中心(Columbia University Medical Center)科学家最新的脑部扫描研究，实际上这涉及到复杂的生物系统。
Corbis这一研究成果刊登在本月的《临床研究期刊》(Journal of Clinical Investigation)上。研究报告的主要作者麦克尔•罗森巴姆(Michael Rosenbaum)表示，简单的说，这是因为你减肥之后会对食物有更多的情绪反应，同时对这种反应的控制力也会下降。
但在脑部血流量如何与行为产生联系的问题上，仍有许多未解之谜。该研究报告的合着者之一鲁道夫•利贝尔(Rudolph Leibel)说，“我无法看着扫描就断言你30秒内会吃根香蕉”。利贝尔上个世纪90年代曾在洛克菲勒大学(Rockefeller University)参与了瘦素的发现。他还说，这进一步表明，减肥后瘦素的变化引发人体明显的生物学变化，通过强大的双重机制实现体重反弹。他介绍称，研究对象一方面显得更加饥饿，另一方面能量消耗降低，这为体重反弹创造了绝佳条件。
科学家认为，瘦素仍可能被用来帮助维持体重不反弹。科学家现在认为保持体重不反弹和减肥是两种不同的机制。圣地亚哥的Amylin Pharmaceuticals Inc.于2006年从Amgen Inc.购买了瘦素的专利权，目前正在对瘦素和糖尿病药物普兰林（月太）联合作用的效果进行试验。大规模人体试验最早将于明年开始。