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FASEB J:解码发胖机制

来源:本站 作者:admin 浏览:798 更新时间:2016-09-10

FASEB J:解码发胖机制

罗切斯特大学研究人员认为,他们在解决体重增加奥秘的机制中获得重大突破。他们发现一种蛋白质Thy1在控制一个原始细胞是否决定成为脂肪细胞中有一个基本的作用,这就使得Thy1成为一个可能的治疗目标,相关研究已经发表在FASEB Journal上。

主要作者Richard P. Phipps博士表示:事实上,一些减肥药包括抗抑郁药或抗成瘾药物,并没有在分子水平上解决脂肪细胞的堆积。尽管40年前就已经发现Thy1,在其他情况下其已被研究,但它的真实分子功能却是未知的。Phipps实验室首次报道在脂肪细胞发育过程中Thy1表达缺失,这表明肥胖可以通过恢复Thy1来治疗。

他们也正在努力开发一种抗肥胖药物,Thy1肽,其发明已申请了国际专利保护。自1989年以来,Phipps一直在调查Thy1。研究的目标是防止或减少肥胖,我们已经展示了如何做到这一点的基本原则。我们相信,体重增加不一定只是吃的越来越少或锻炼的一个结果。我们的重点是参与脂肪细胞发育的复杂网络。

研究人员研究了小鼠和人来源的细胞系,确认Thy1功能的缺失会促进更多的脂肪细胞。缺乏Thy1蛋白质小鼠、喂食高脂肪饮食后,相比于也吃相同高脂肪饮食的正常对照组小鼠,获得了更多的重量。

Phipps和他的同事正在继续调查为什么细胞有潜力能转化脂肪细胞以及为什么当Thy1关闭脂肪会积累更快。目前尚不清楚是否Thy1的水平在不同人出生时就不同,或者Thy1的水平是否由于时间发展和暴露于各种环境因素而改变。

为了解决后一个问题,Phipps实验室分别研究化学品即被称为肥胖基因如双酚A(BPA),阻燃剂和邻苯二甲酸盐是否能减少人体细胞Thy1的表达,促进肥胖。

原文链接:Thy1 (CD90) controls adipogenesis by regulating activity of the Src family kinase, Fyn

原文摘要:Worldwide obesity rates are at epidemic levels, and new insight into the regulation of obesity and adipogenesis are required. Thy1 (CD90), a cell surface protein with an enigmatic function, is expressed on subsets of fibroblasts and stem cells. We used a diet-induced obesity model to show that Thy1-null mice gain weight at a faster rate and gain 30% more weight than control C57BL/6 mice. During adipogenesis, Thy1 expression is lost in mouse 3T3-L1 cells. Overexpression of Thy1 blocked adipocyte formation and reduced mRNA and protein expression of an adipocyte marker, fatty acid-binding protein 4, by 5-fold. Although preadipocyte fibroblasts expressed Thy1 mRNA and protein, adipocytes from mouse and human fat tissue had almost undetectable Thy1 levels. Thy1 decreases the activity of the adipogenic transcription factor PPARγ by more than 60% as shown by PPARγ-dependent reporter assays. Using both genetic and pharmacologic approaches, we show Thy1 expression dampens PPARγ by inhibiting the activity of the Src-family kinase, Fyn. Thus, these studies reveal Thy1 blocks adipogenesis and PPARγ by inhibiting Fyn and support the idea that Thy1 is a novel therapeutic target in obesity.—Woeller, C. F., O’loughlin, C. W., Pollock, S. J., Thatcher, T. H., Feldon, S. E., and Phipps, R. P. Thy1 (CD90) controls adipogenesis by regulating activity of the Src family kinase, Fyn.

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