美國(guó)丹納—法伯癌癥研究所確認(rèn)了一種雙單元分子開關(guān),，它可成功操控小鼠和人類細(xì)胞生成棕色脂肪,。專家認(rèn)為,，這項(xiàng)研究將有助于開發(fā)治療肥胖癥和糖尿病的新方法。相關(guān)研究成果刊登在近期出版的《自然》雜志網(wǎng)絡(luò)版上,。
人體脂肪分為白色和棕色兩種,。白色脂肪細(xì)胞會(huì)存儲(chǔ)攝入體內(nèi)的多余熱量，如在體內(nèi)積聚過(guò)多,，就會(huì)形成肥胖,。棕色脂肪則是一種天然耗能型脂肪，對(duì)于維持體溫和能量平衡起著重要作用,，其細(xì)胞中含有大量的線粒體,，可通過(guò)燃燒攝入的糖來(lái)產(chǎn)生熱量，而不是以脂肪形式將其存儲(chǔ)起來(lái),。過(guò)去,，科學(xué)家們一直認(rèn)為，棕色脂肪僅存于嬰幼兒體內(nèi),，之后會(huì)逐漸消失,，成人體內(nèi)殘存的數(shù)量很少。但最近研究人員通過(guò)正電子發(fā)射斷層掃描（PET）發(fā)現(xiàn),，在成人的頸部和胸部區(qū)域散布著大量的棕色脂肪,。
美國(guó)丹納—法伯癌癥研究所的布魯斯·斯皮格爾曼博士領(lǐng)導(dǎo)的研究小組發(fā)現(xiàn)，PRDM16蛋白會(huì)與C/EBP-beta蛋白一起構(gòu)成雙單元開關(guān),，能夠?qū)⑴咛ブ衅渌愋偷募?xì)胞變成棕色脂肪細(xì)胞,。研究人員利用病毒把這種雙單元開關(guān)分別植入胚胎小鼠的結(jié)締組織細(xì)胞、成年小鼠的皮細(xì)胞以及取自新生兒包皮的皮細(xì)胞之中,。在這三項(xiàng)實(shí)驗(yàn)中,，雙單元開關(guān)都促使這些纖維原細(xì)胞產(chǎn)生成熟的棕色脂肪細(xì)胞。隨后,，他們將這些被稱為eBAT的合成棕色脂肪前體細(xì)胞移植到成年小鼠體內(nèi),，用以生成棕色脂肪組織。經(jīng)PET掃描證實(shí),，成年小鼠體內(nèi)新生的棕色脂肪組織會(huì)燃燒掉體內(nèi)多余的能量,，從而避免了這些能量以脂肪形式儲(chǔ)存在白色脂肪細(xì)胞之中,。
斯皮格爾曼表示，實(shí)驗(yàn)證明,，操控棕色脂肪生成機(jī)制的開關(guān)有可能是一種對(duì)付人類肥胖癥和糖尿病的潛在手段,。從病人體內(nèi)移除一些組織，加入PRDM16-C/EBP開關(guān)后再重新移植到病人體內(nèi),，就可生成更多的棕色脂肪,。而如能開發(fā)出一種新藥來(lái)提高人體內(nèi)的棕色脂肪含量,，則無(wú)需進(jìn)行移植,，這將會(huì)是一個(gè)直接、有效的減肥方式,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 29 July 2009 | doi:10.1038/nature08262
Initiation of myoblast to brown fat switch by a PRDM16–C/EBP- transcriptional complex
Shingo Kajimura1,2, Patrick Seale1,2, Kazuishi Kubota2, Elaine Lunsford3, John V. Frangioni3, Steven P. Gygi2 & Bruce M. Spiegelman1,2
1 Dana-Farber Cancer Institute,
2 Department of Cell Biology, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
3 Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
Brown adipose cells are specialized to dissipate chemical energy in the form of heat, as a physiological defence against cold and obesity1. PRDM16 (PR domain containing 16) is a 140 kDa zinc finger protein that robustly induces brown fat determination and differentiation2. Recent data suggests that brown fat cells arise in vivo from a Myf5-positive, myoblastic lineage by the action of PRDM16 (ref. 3); however, the molecular mechanisms responsible for this developmental switch is unclear. Here we show that PRDM16 forms a transcriptional complex with the active form of C/EBP-(also known as LAP), acting as a critical molecular unit that controls the cell fate switch from myoblastic precursors to brown fat cells. Forced expression of PRDM16 and C/EBP- is sufficient to induce a fully functional brown fat program in naive fibroblastic cells, including skin fibroblasts from mouse and man. Transplantation of fibroblasts expressing these two factors into mice gives rise to an ectopic fat pad with the morphological and biochemical characteristics of brown fat. Like endogenous brown fat, this synthetic brown fat tissue acts as a sink for glucose uptake, as determined by positron emission tomography with fluorodeoxyglucose. These data indicate that the PRDM16–C/EBP- complex initiates brown fat formation from myoblastic precursors, and may provide opportunities for the development of new therapeutics for obesity and type-2 diabetes.
