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【Nature】以脂肪燃烧脂肪

用脂肪来燃烧脂肪?听起来像是天方夜谭,然而哈佛医学院的最新研究证明,一种鲜为人知的脂肪组织——红脂肪(brown fat)可以燃烧卡路里,影响机体的能量代谢系统,有效减轻体重。

在大多数人看来,除了能够保持体温和贮存能量之外,脂肪对人体来说几乎是有害无益。然而事实上,人体内存在两种不同的脂肪:白脂肪与红脂肪。白脂肪一直以来便是令节食者无可奈何的罪魁祸首,然而红脂肪却与之截然不同,它不仅含有大量的线粒体(mitochondria)——一种相当于能量生产机器的人体细胞,它能燃烧卡路里以提供热量。

婴儿体内含有大量的红脂肪以维持体温,然而在成年人体内,红脂肪却几乎是无迹可寻。通过基因实验,科学家证明,一些所谓的肌肉前体细胞(muscle precursor cell)也有可能转变为红脂肪。

哈佛医学院的细胞生物学家布鲁斯·斯皮格曼(Bruce Spiegelman)的早期研究证明,加入PRDM16基因可使白脂肪转化为红脂肪。在被抽取的脂肪或肌肉前体细胞内植入触发型基因(genetic trigger)便可在人体内形成红脂肪供应系统,迅速燃烧多余的脂肪。

作为《自然》杂志上红脂肪论文的合著者之一的斯皮格曼认为,理论上,这项技术可以影响整个机体的能量代谢系统。对于这项技术是否会阻碍肌肉形成的疑问,他表示,肌肉前体细胞可以自我增殖。当少量细胞变异为红脂肪后,留下的空位很快便会为新生细胞所填补。

哈佛大学医学院的曾玉华(Yu-Hua Tseng)和罗纳德·卡恩(C. Ronald Kahn)领导下的另一研究小组则发现了影响红细胞形成的另一关键因素—— BMP7基因。当老鼠体内的BMP7过量时,将会产生大量红细胞,而白细胞却几乎停止了增长。因此,红细胞增加,随着由此导致的机体耗能的增加,实验老鼠的体重也明显减轻。

目前这些发现仅局限于实验室里的小白鼠,一旦证实它们同样适用于人类,这项技术将为人们保持体型提供新的捷径,减肥人士亦无须再忍受节食之苦。斯德哥尔摩大学(University of Stockholm)的脂肪细胞专家芭芭拉·坎农(Barbara Cannon)分析指出,这些研究成果使人们向最终目标迈出了关键的一步——使红脂肪族成为抵御肥胖症的有效手段。

不过,曾玉华强调说,目前对于一般人而言,节食和运动仍是减肥的最佳手段。然而对于那些遗传性肥胖症患者来说,注射BMP7为他们恢复健康体型带来了新的希望。作为基因触发药物的开发者之一,斯皮格曼亦建议人们谨慎行事。他表示,目前仍不能确定发挥减肥功效所需的红脂肪具体数量是多少。对于人类而言,这项技术尚未完全成熟,然而不管怎样,这是一个振奋人心的好消息

转自《第一财经日报》

Nature 454, 1000-1004 (21 August 2008) | doi:10.1038/nature07221

New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure

Yu-Hua Tseng1, Efi Kokkotou3, Tim J. Schulz1, Tian Lian Huang1, Jonathon N. Winnay1, Cullen M. Taniguchi1, Thien T. Tran1, Ryo Suzuki1, Daniel O. Espinoza1, Yuji Yamamoto1, Molly J. Ahrens4, Andrew T. Dudley4, Andrew W. Norris5, Rohit N. Kulkarni2 & C. Ronald Kahn1 听这个题目挺有意思的,看了下主要是BMP-7的作用,特附引言(摘要)部分及全文供对这方面有兴趣的战友阅读。

题目:
New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure


摘要:
Adipose tissue is central to the regulation of energy balance. Two functionally different types of fat are present in mammals: white adipose tissue, the primary site of triglyceride storage, and brown adipose tissue, which is specialized in energy expenditure and can counteract obesity. Factors that specify the developmental fate and function of white and brown adipose tissue remain poorly understood. Here we demonstrate that whereas some members of the family of bone morphogenetic proteins (BMPs) support white adipocyte differentiation, BMP7 singularly promotes differentiation of brown preadipocytes even in the absence of the normally required hormonal induction cocktail. BMP7 activates a full program of brown adipogenesis including induction of early regulators of brown fat fate PRDM16 (PR-domain-containing 16) and PGC-1 (peroxisome proliferator-activated receptor- (PPAR) coactivator-1), increased expression of the brown-fat-defining marker uncoupling protein 1 (UCP1) and adipogenic transcription factors PPAR and CCAAT/enhancer-binding proteins (C/EBPs), and induction of mitochondrial biogenesis via p38 mitogen-activated protein (MAP) kinase-(also known as Mapk14) and PGC-1-dependent pathways. Moreover, BMP7 triggers commitment of mesenchymal progenitor cells to a brown adipocyte lineage, and implantation of these cells into nude mice results in development of adipose tissue containing mostly brown adipocytes. Bmp7 knockout embryos show a marked paucity of brown fat and an almost complete absence of UCP1. Adenoviral-mediated expression of BMP7 in mice results in a significant increase in brown, but not white, fat mass and leads to an increase in energy expenditure and a reduction in weight gain. These data reveal an important role of BMP7 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro, and provide a potential new therapeutic approach for the treatment of obesity.

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作者:admin@医学,生命科学    2010-12-21 17:11
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