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.'

沒錯，你減少飲食又加強鍛煉，終于成功減輕了體重。但現(xiàn)在體重又在逐漸反彈。你比任何時候都感到饑餓，似乎抵擋不了食物的誘惑。減肥計劃又失敗了，這全是你的錯，對嗎？

錯�，F(xiàn)在你可以將其怪罪于人類的進化�；仡櫲祟悮v史，絕大部分時間，饑餓對人造成的威脅都要超過肥胖。表面上看，你是缺乏意志力才導(dǎo)致減肥后體重反彈；但根據(jù)哥倫比亞大學(xué)醫(yī)學(xué)中心(Columbia University Medical Center)科學(xué)家最新的腦部掃描研究，實際上這涉及到復(fù)雜的生物系統(tǒng)。

Corbis這一研究成果刊登在本月的《臨床研究期刊》(Journal of Clinical Investigation)上。研究報告的主要作者麥克爾•羅森巴姆(Michael Rosenbaum)表示，簡單的說，這是因為你減肥之后會對食物有更多的情緒反應(yīng)，同時對這種反應(yīng)的控制力也會下降。

在這個系統(tǒng)中，主要的推動力是瘦素(leptin)，這是脂肪細(xì)胞分泌的一種激素。當(dāng)人或嚙齒類動物體重下降10%或更多時，瘦素的水平就會急劇下降，引發(fā)一連串的生理變化，促使體重回升。在這個過程中，骨骼肌會更加有效地工作，甲狀腺等激素的分泌也會相應(yīng)下降，因此身體可以減少15%-20%的熱量消耗。

羅森巴姆表示，假設(shè)兩個人體重相同，但其中一個是體重下降10%才達(dá)到這一水平，那么這個人每天需要多消耗300-400卡路里，或少攝入300-400卡路里的熱量才能維持當(dāng)前體重。這一熱量足以使他一年體重反彈超過11公斤。

無論你在減肥前是肥胖還是相對苗條，這一機制都會發(fā)揮作用；研究人員相信這一影響可以持續(xù)數(shù)年。但在此前研究中，研究對象攝入瘦素替代品后，成功地逆轉(zhuǎn)了這一新陳代謝變化過程，進而保持了減肥成果。實際上，瘦素替代品“欺騙”了他們的身體，讓身體忽略了曾經(jīng)減肥的事實。

最新研究顯示，減肥帶來的這一新陳代謝變化也反映在大腦活動的變化上。哥倫比亞大學(xué)醫(yī)學(xué)中心的研究人員對六位采用流食的肥胖癥住院患者的進食量進行了精確控制。這些患者的體重都下降了10%，被分成使用瘦素的試驗組和使用安慰劑的對照組。研究人員利用功能性核磁共振成像技術(shù)(MRI)，觀察患者在各個階段看到食物與非食物時的腦部活動。

掃描結(jié)果顯示，研究對象在減肥后，其腦部和食物有關(guān)的情緒與感覺反應(yīng)區(qū)域血流量加大，而和控制進食有關(guān)的區(qū)域的血流量減少。當(dāng)研究對象攝入瘦素替代品后，這類變化就被逆轉(zhuǎn)，腦部活動重新回到減肥之前的狀態(tài)。

但在腦部血流量如何與行為產(chǎn)生聯(lián)系的問題上，仍有許多未解之謎。該研究報告的合著者之一魯?shù)婪?bull;利貝爾(Rudolph Leibel)說，“我無法看著掃描就斷言你30秒內(nèi)會吃根香蕉”。利貝爾上個世紀(jì)90年代曾在洛克菲勒大學(xué)(Rockefeller University)參與了瘦素的發(fā)現(xiàn)。他還說，這進一步表明，減肥后瘦素的變化引發(fā)人體明顯的生物學(xué)變化，通過強大的雙重機制實現(xiàn)體重反彈。他介紹稱，研究對象一方面顯得更加饑餓，另一方面能量消耗降低，這為體重反彈創(chuàng)造了絕佳條件。

研究人員最初認(rèn)為，瘦素能向人體發(fā)出停止進食的信號，并希望將其用作減肥藥。但實際上，瘦素的作用是阻止體重下降，瘦素水平的下降會使人體進入生存模式，這是人體應(yīng)對食物匱乏、脂肪儲存下降的不利狀況的運轉(zhuǎn)模式。從進化角度來說，這一反應(yīng)機制合情合理，但面對現(xiàn)代的肥胖問題卻適得其反。利貝爾說，回顧人類歷史，大多數(shù)時間人類都需要消耗大量能量去獲取食物；而現(xiàn)在你只需一個電話就可以召來取之不盡的食物。

科學(xué)家認(rèn)為，瘦素仍可能被用來幫助維持體重不反彈�？茖W(xué)家現(xiàn)在認(rèn)為保持體重不反彈和減肥是兩種不同的機制。圣地亞哥的Amylin Pharmaceuticals Inc.于2006年從Amgen Inc.購買了瘦素的專利權(quán)，目前正在對瘦素和糖尿病藥物普蘭林（月太）聯(lián)合作用的效果進行試驗。大規(guī)模人體試驗最早將于明年開始。

與此同時，有些人又是怎樣克服這一生物系統(tǒng)，成功保持體重的呢？通常來說，這些人會非常小心地控制飲食，并繼續(xù)加強身體鍛煉。羅森巴姆說，任何減肥后又成功保持身材的人都會告訴你，他們的秘密就是堅持。這些成功者戰(zhàn)勝了生物系統(tǒng)，他們值得我們最高程度的欽佩與尊敬。