生物谷报道：为了减肥，你是不是对美味食物垂涎欲滴却不敢张口呢？好消息来了！美国科学家近日通过灭活小鼠的一个关键基因，使得它能疯狂摄取食物却不增长体重。这一研究有望帮助人们在遍尝美味食物的同时保持苗条的体形，并为治疗肥胖和糖尿病提供了希望。相关论文发表于9月5日的《细胞－代谢》（Cell Metabolism）上。
之前有研究发现，食用高蛋白食物或是补充亮氨酸（leucine）能减轻体重，但是其中的机制一直没有弄清。
在最新的研究中，美国宾夕法尼亚州立大学的Christopher Lynch和同事灭活了小鼠体内的一个基因，该基因的作用是清除血液中的亮氨酸。结果发现，这些小鼠比正常小鼠表现得更为饥饿，吃得更多。当喂以高脂肪食物后，这些小鼠并没有像正常小鼠那样发胖，而是仍旧保持瘦小，身上的脂肪大约只有正常小鼠的一半。当喂以正常食物后，这些小鼠看起来更为健康，体重比正常小鼠要低10％左右，患糖尿病的风险也比正常小鼠要低。Lynch推测，这些小鼠疯狂进食的原因大概是，利用体内的亮氨酸水平来决定该吃多少以达到最适宜的体重。
造成这一结果的原因在于对亮氨酸的抑制被解除了。被灭活的基因所编码的酶能够分解亮氨酸，此基因被灭活后导致亮氨酸在体内积累，刺激细胞产生新的多余的蛋白质并将它们分解掉。这种无效循环（futile cycle）燃烧了过剩的能量，所以小鼠大吃特吃却仍然能够保持体形。
美国马里兰大学内分泌学和营养学研究人员Susan Fried认为，此次研究表明了补充亮氨酸能导致长期的体重减轻。但是消耗能量的关键在于停止体内亮氨酸的代谢，而不是增加亮氨酸的摄取。理论上可以通过开发一种药物来阻止这种酶分解亮氨酸，但是是否会带来副作用还有待研究。Fried表示，要将这一研究应用于肥胖等症的实际治疗，还有很长一段路要走。
看来，减肥者要减去多余脂肪的话，至少目前一段时间还需要去健身房里进行锻炼。（科学网 梅进/编译）
原始出处:
Cell Metabolism, Vol 6, 181-194, 05 September 2007
Article
Disruption of BCATm in Mice Leads to Increased Energy Expenditure Associated with the Activation of a Futile Protein Turnover Cycle
Pengxiang She,1 Tanya M. Reid,3 Sarah K. Bronson,1 Thomas C. Vary,1 Andras Hajnal,2 Christopher J. Lynch,1, and Susan M. Hutson3
1 Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
2 Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
3 Department of Biochemistry and Molecular Biology, Nutrition Research Center, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA
Corresponding author
Christopher J. Lynch
clynch@psu.edu
Leucine is recognized as a nutrient signal; however, the long-term in vivo consequences of leucine signaling and the role of branched-chain amino acid (BCAA) metabolism in this signaling remain unclear. To investigate these questions, we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism. BCATm−/− mice exhibited elevated plasma BCAAs and decreased adiposity and body weight, despite eating more food, along with increased energy expenditure, remarkable improvements in glucose and insulin tolerance, and protection from diet-induced obesity. The increased energy expenditure did not seem to be due to altered locomotor activity, uncoupling proteins, sympathetic activity, or thyroid hormones but was strongly associated with food consumption and an active futile cycle of increased protein degradation and synthesis. These observations suggest that elevated BCAAs and/or loss of BCAA catabolism in peripheral tissues play an important role in regulating insulin sensitivity and energy expenditure.
