从苍蝇的肥胖中得到的启示

2006-01-11 00:00 来源:医药生命科学动态跟踪 作者:hermean 编译
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从苍蝇的肥胖中得到启示
最新的研究表明,昆虫储藏脂肪的方式和哺乳动物是一样的,这种机制共同点的发现有助于科学家去发明与肥胖抗争的新方法。
脂肪细胞的形成来源于干细胞分化过程中的一个“决定”。干细胞可能变成成骨细胞或者前成脂肪细胞,如果是后者,将导致脂肪细胞数目的增长。但究竟这种分化的是何种信号,目前还不得而知。
得克萨斯大学的分子生物学家Jonathan Graff研究了一组“刺猬”基因,它们被认为是会影响人及苍蝇和许多别的生物的发育。Graff通过对“刺猬”基因进行突变来研究它对脂肪细胞的影响。苍蝇失掉这些基因后,变得更胖,抗饥饿的能力也有所增强,总体脂肪及相关脂蛋白水平也要高于野生型的对照组。这项成果发表在本月的Cell Metabolism上。
“刺猬”基因在老鼠身上似乎也有同样的功能。当鼠的干细胞暴露在“刺猬”基因表达的阴断剂中时,脂肪细胞量上升。反过来,提高“刺猬”基因的表达,则变成了骨细胞。这有可能可以解释为什么人变老的时候骨质变疏松,而脂肪细胞却在增多。
哈佛医学院的Barbara Kahn教授认为,这些有趣的发现以及“刺猬”基因机制有可能对将来骨质疏松及肥胖的药物治疗都提供帮助。

摘自ScienceNOW,2006-1-10
原文链接:http://sciencenow.sciencemag.org/cgi/content/full/2006/110/3
原文:
Fat Flies and Rotund Rodents
By Amy R. Coombs
ScienceNOW Daily News
10 January 2006

As anyone on a new year's diet can attest, gaining weight is much easier than burning it off. Humans aren't the only ones capable of packing on the pounds, however. New research indicates that insects store fat in one of the same ways mammals do. Identifying the fat management pathways insects and mammals have in common may eventually help scientists develop new ways to fight obesity, say the researchers.
Fat cells form when a unique class of stem cells make a critical decision: They either become osteoblasts, which develop into bone cells, or preadipocytes, which give rise to fat cells. Exactly which messages tell a stem cell to become a fat cell rather than a bone cell remain a mystery, however.

To learn more about the process, Jonathan Graff, a molecular biologist at the University of Texas Southwestern Medical Center in Dallas, studied a set of genes known to impact development in humans, flies, and many other animals. To see if the set, called the Hedgehog suite, also influences the development of fat cells, Graff and his research team bred mutant flies missing select Hedgehog genes. Flies without the genes were fatter, survived starvation better, and had higher overall levels of lipid and fat related proteins than did flies with an intact gene suite, the team reports this month in Cell Metabolism.

The Hedgehog genes appear to play a similar role in mice. When the researchers exposed mouse stem cells to drugs that prevent some of these genes from working, the cells gave rise to fat cells. When, on the other hand, the team expressed the Hedgehog genes at higher than normal levels in these stem cells, the cells became bone cells instead. Graff says this discovery might help explain why people tend to gain weight while losing bone mass as they age. These results are the first indication that Hedgehog genes regulate fat and bone cell formation, he says, and the first example of an insect and a mammal having the same fat regulatory pathways.

The findings are intriguing, says Barbara Kahn, a professor of medicine at Harvard Medical School, but they only scratch the surface of the complex cellular message systems that regulate fat cell formation in mammals. "It's possible the Hedgehog pathway might one day be harnessed for drug treatments that target osteoporosis and obesity," she says, "but to really be clear about its role in physiology, one would need to do more research."

Related sites

More on the Hedgehog pathway
Center for Disease Control and Prevention obesity resources
Medline resource page about obesity
Graff Lab site

编辑: Zhu

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