高蛋白膳食可以通过抑制短期食欲来防止体重增加，但生理学水平上高蛋白膳食如何发挥这种作用，至今仍是一个迷。现在一项新研究或许为解开这个迷提供了一把钥匙。研究发现了一种微小的蛋白质片段，名为YY3-36肽（PYY3-36）。这种肽可以对高水平的膳食蛋白做出反应从而抑制饥饿。
2002年8月，伦敦帝国学院的内分泌学家Stephen Bloom和同事们展示了他们的研究结果。他们将PYY3-36注入啮齿动物和人体内，发现它能够在12个小时甚至更长时间内抑制饥饿的感觉。还可以防止啮齿动物体重的增加，这或许是个预兆：YY3-36有可能成为一种潜在的抗肥胖新药。然而并不是所有的研究小组都能重复得到这些结果，这使得这种肽类的未来多少有些尴尬。
伦敦大学学院的内分泌学家Rachel Batterham 曾是Bloom研究小组的成员。他和他的同事们另辟蹊径，从另一个角度切入了这个问题。他们首先让志愿者分别服用高蛋白，高碳水化合物或高脂肪的食物，然后观察他们饥饿的感觉。这些志愿者均为男性，体重或正常或肥胖。与期望的结果一致，相比服用其它食物的志愿者，高蛋白食物组在餐后三个小时里饥饿感明显更弱，而且他们血液中PYY3-36的水平也是各组中最高的。在小鼠中做的同类实验也显示了相似的结果，与啮齿动物血液中PYY3-36水平较高相一致的是大脑中一类由肥胖诱导蛋白质，它们的mRNA水平也呈下降趋势。
研究小组构建了一种缺乏PYY基因的基因敲除小鼠。敲除小鼠体重肥胖且酷爱进食。10周大小的敲除小鼠要比它们的正常同类重37.5%，体内脂肪也要多12%。高蛋白膳食并不能抑制它们的饥饿感。给这些敲除小鼠注射了PYY3-36后，它们的食量和体内脂肪以及体重出现了戏剧性的下降，而给予同样治疗的野生型正常同类的这些特征则没有或很少发生改变。研究者们的结果发表在这个月的《Cell Metabolism（细胞代谢）》上。
这项新研究并没有完全解决问题。“其中仍有存在争议的部分。”波士顿Beth Israel Deaconess医学中心的内分泌学家Jeffrey Flier说道。PYY水平和蛋白膳食之间的关系得到了“研究数据的充分支持”，但根据此前另外两个研究小组的结果，他们甚至没有得到和PYY基因敲除小鼠稍有不同的肥胖表型，因此未来还需要更多的工作来抚平这些差异。
http://sciencenow.sciencemag.org/cgi/content/full/2006/906/2
Hello Protein, Goodbye Fat
A high protein diet can prevent weight gain by curbing short-term appetite. But just how this diet works on a physiological level has remained a mystery. Now, a new study suggests that the key is a tiny protein fragment called peptide YY3-36 (PYY3-36), which dampens hunger in response to high levels of dietary protein.
In August 2002, endocrinologist Stephen Bloom and colleagues at Imperial College London showed that when they injected PYY3-36 into rodents and humans, it decreased hunger for 12 hours or more. Rodents on the peptide also curbed their weight gain, leading some to herald PYY3-36 as a potential new anti-obesity drug. However, not all groups have been able to replicate these results, leaving the peptide's promise in the lurch.
A former member of Bloom's team, endocrinologist Rachel Batterham of the University College London and colleagues, took another stab, this time from a different angle. They first fed a group of normal-weight and obese men a diet high in either protein, carbohydrate, or fat. As expected, volunteers on the high-protein diet felt significantly less hungry than those on the other diets for up to 3 hours after the meal. The high-protein dieters also had the highest levels of PYY3-36 in their blood than the other dieters. Mice showed similar effects, and high blood levels of PYY3-36 in the rodents corresponded to a reduction in the mRNA levels of certain fatness-inducing messenger proteins in the brain.
To seal the deal, the team created a knockout mouse that lacked the PYY gene. The knockouts were obese and loved to eat: by 10 weeks of age, PYY knockout mice weighed about 37.5% more than normal mice and had about 12% more body fat. A high-protein diet did not curb their hunger. Giving PYY3-36 to the knockout mice led to a drastic reduction in their eating habits and consequently their body fat and body weight. The wild-type mice showed little or no change with the same treatment, the researchers report in this month's issue of Cell Metabolism.
The new study hasn't entirely settled things. "There are still elements of controversy," says endocrinologist Jeffrey Flier at the Beth Israel Deaconess Medical Center in Boston, Massachusetts. The relationship between PYY levels and dietary protein is "extremely well supported by the data," he says, but in the light of previous work by two other groups who failed to get an obese phenotype with slightly different PYY knockout mice, future work is needed to reconcile this discrepancy.
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