生物谷報道：為了減肥,，你是不是對美味食物垂涎欲滴卻不敢張口呢,？好消息來了！美國科學家近日通過滅活小鼠的一個關(guān)鍵基因,，使得它能瘋狂攝取食物卻不增長體重,。這一研究有望幫助人們在遍嘗美味食物的同時保持苗條的體形，并為治療肥胖和糖尿病提供了希望,。相關(guān)論文發(fā)表于9月5日的《細胞－代謝》（Cell Metabolism）上,。
之前有研究發(fā)現(xiàn)，食用高蛋白食物或是補充亮氨酸（leucine）能減輕體重,，但是其中的機制一直沒有弄清,。
在最新的研究中，美國賓夕法尼亞州立大學的Christopher Lynch和同事滅活了小鼠體內(nèi)的一個基因,，該基因的作用是清除血液中的亮氨酸,。結(jié)果發(fā)現(xiàn),，這些小鼠比正常小鼠表現(xiàn)得更為饑餓，吃得更多,。當喂以高脂肪食物后,，這些小鼠并沒有像正常小鼠那樣發(fā)胖，而是仍舊保持瘦小,，身上的脂肪大約只有正常小鼠的一半,。當喂以正常食物后，這些小鼠看起來更為健康,，體重比正常小鼠要低10％左右,，患糖尿病的風險也比正常小鼠要低。Lynch推測,，這些小鼠瘋狂進食的原因大概是,，利用體內(nèi)的亮氨酸水平來決定該吃多少以達到最適宜的體重。
造成這一結(jié)果的原因在于對亮氨酸的抑制被解除了,。被滅活的基因所編碼的酶能夠分解亮氨酸,，此基因被滅活后導致亮氨酸在體內(nèi)積累，刺激細胞產(chǎn)生新的多余的蛋白質(zhì)并將它們分解掉,。這種無效循環(huán)（futile cycle）燃燒了過剩的能量,，所以小鼠大吃特吃卻仍然能夠保持體形。
美國馬里蘭大學內(nèi)分泌學和營養(yǎng)學研究人員Susan Fried認為,，此次研究表明了補充亮氨酸能導致長期的體重減輕,。但是消耗能量的關(guān)鍵在于停止體內(nèi)亮氨酸的代謝，而不是增加亮氨酸的攝取,。理論上可以通過開發(fā)一種藥物來阻止這種酶分解亮氨酸,，但是是否會帶來副作用還有待研究。Fried表示,，要將這一研究應用于肥胖等癥的實際治療,，還有很長一段路要走。
看來,，減肥者要減去多余脂肪的話,，至少目前一段時間還需要去健身房里進行鍛煉。（科學網(wǎng) 梅進/編譯）
原始出處:
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
[email protected]
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.
