院士《Nature》续写08年十大突破 脂肪助你keep fit

　　

生物通报道，哈佛大学医学院细胞生物学系，Dana-Farber癌症研究所，Beth Israel医学研究中心的科学家在棕色脂肪的研究方面再度取得新成果，文章Initiation of myoblast to brown fat switch by a PRDM16–C/EBP- transcriptional complex发表在Nature在线版上。

 

文章通讯作者是美国科学院院士Bruce M. Spiegelman，哈佛大学医学院的教授，2008年，他曾发现棕色脂肪的转换开关蛋白，这一成果被Science杂志评为年度十大突破之一。

 

神奇的棕色脂肪

脂肪大概是所有爱美女性所痛恨的，男性大概也不例外。

 

其实，脂肪也有好坏之分，脂肪分两类，一类白色脂肪，一类棕色脂肪，白色脂肪储能，棕色脂肪消耗卡路里。可惜，人成年后，棕色脂肪比例极少，大部分的脂肪都是白色脂肪，也就是白花花的肚腩肉之类的。

 

2008年，院士Bruce M. Spiegelman曾发现PRDM16可以讲肌肉细胞转换成棕色脂肪，首次找到棕色脂肪的转换开关。科学家们也就开始期待，某天可以将多余的白色脂肪通过这种改变转化为棕色脂肪，让肥胖消失殆尽，让糖尿病等肥胖疾病消失殆尽。

 

仅发现这个开关是不够的，还需要有进一步了解转换的机制，才便于科学家进行认为的改造。

 

历时一年，Bruce M. Spiegelman院士再度取得突破，他的研究小组发现PRDM16蛋白与C/EBPβ蛋白结合在一起发挥开关功能。经过调节能够将胚胎中其他类型的细胞变成棕色脂肪细胞。

 

研究小组用病毒载体将PRDM16-C/EBPβ导入小鼠胚胎组织的结缔组织细胞、成年小鼠的皮肤细胞和新生儿的包皮细胞中。结果发现，成功转染PRDM16-C/EBPβ的细胞均转化为棕色脂肪细胞。

 

Bruce M. Spiegelman院士认为，这可能会是一种更为有效、更为健康的减肥方式。为肥胖症、糖尿病等多种代谢疾病带来新的希望。

（生物通 小茜）

生物通推荐原文检索

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

 

Dana-Farber Cancer Institute,

Department of Cell Biology, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA

Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA

 

【Abstract】

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.