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Nature:一种双单元分子开关可控棕色脂肪细胞生成

来源:科技日报 2009-08-17 09:18

专题:Nature报道

美国丹纳—法伯癌症研究所确认了一种双单元分子开关,它可成功操控小鼠和人类细胞生成棕色脂肪。专家认为,这项研究将有助于开发治疗肥胖症和糖尿病的新方法。相关研究成果刊登在近期出版的《自然》杂志网络版上。

人体脂肪分为白色和棕色两种。白色脂肪细胞会存储摄入体内的多余热量,如在体内积聚过多,就会形成肥胖。棕色脂肪则是一种天然耗能型脂肪,对于维持体温和能量平衡起着重要作用,其细胞中含有大量的线粒体,可通过燃烧摄入的糖来产生热量,而不是以脂肪形式将其存储起来。过去,科学家们一直认为,棕色脂肪仅存于婴幼儿体内,之后会逐渐消失,成人体内残存的数量很少。但最近研究人员通过正电子发射断层扫描(PET)发现,在成人的颈部和胸部区域散布着大量的棕色脂肪。

美国丹纳—法伯癌症研究所的布鲁斯·斯皮格尔曼博士领导的研究小组发现,PRDM16蛋白会与C/EBP-beta蛋白一起构成双单元开关,能够将胚胎中其他类型的细胞变成棕色脂肪细胞。研究人员利用病毒把这种双单元开关分别植入胚胎小鼠的结缔组织细胞、成年小鼠的皮细胞以及取自新生儿包皮的皮细胞之中。在这三项实验中,双单元开关都促使这些纤维原细胞产生成熟的棕色脂肪细胞。随后,他们将这些被称为eBAT的合成棕色脂肪前体细胞移植到成年小鼠体内,用以生成棕色脂肪组织。经PET扫描证实,成年小鼠体内新生的棕色脂肪组织会燃烧掉体内多余的能量,从而避免了这些能量以脂肪形式储存在白色脂肪细胞之中。

斯皮格尔曼表示,实验证明,操控棕色脂肪生成机制的开关有可能是一种对付人类肥胖症和糖尿病的潜在手段。从病人体内移除一些组织,加入PRDM16-C/EBP开关后再重新移植到病人体内,就可生成更多的棕色脂肪。而如能开发出一种新药来提高人体内的棕色脂肪含量,则无需进行移植,这将会是一个直接、有效的减肥方式。(生物谷Bioon.com)

生物谷推荐原始出处:

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.

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