Network regulation of brown adipocyte lineages

棕色脂肪细胞谱系的网络调控

基本信息

批准号：
23659471
负责人：
MAZDA Osam
金额：
$ 2.5万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Challenging Exploratory Research
财政年份：
2011
资助国家：
日本
起止时间：
2011 至无数据
项目状态：
已结题

项目摘要

Brown adipocytes dissipates fat energy as heat and plays crucial roles in energy expenditure and thermogenesis. They are also involved in regulation of visceral obesity and insulin resistance. The present study aims at devising novel technology to directly reprogram somatic cells such as fibroblasts into brown adipocytes. First, mRNA was obtained from brown adipocytes that had been established from iPS cells and subjected to DNA microarray technology to find out some genes that may have important roles in brown adipocyte lineages. Second, some of the genes identified as above were introduced into fibroblasts that were subsequently cultured under various conditions. Transfection of a particular combination of the genes resulted in generation of cells with multilocular lipid droplet and abundant mitochondria. Some other combinations of genes resulted in more efficient generation of such cells. Characterization of the cells strongly suggested typical features of the brown adipocytes. Interestingly, some different combination of genes induced white adipocytes-like cells more efficiently than brown adipocyte-like cells. These results strongly suggest direct reprogramming of fibroblasts into brown adipocytes by defined factors. We are thus currently analyzing optimal condition of the direct reprogramming as well as molecular mechanisms of the cell fate decision. The present study may contribute not only to the elucidation of differentiation of brown adipocytes but also to technology to generate and characterize brown adipocytes. Such technology may potentially provide novel regenerative medicine to control metabolic syndrome in the future.

棕色脂肪细胞随着热量而消散脂肪能量，并在能量消耗和热生成中起着至关重要的作用。它们还参与了内脏肥胖和胰岛素抵抗的调节。本研究旨在设计新型技术，以将诸如成纤维细胞等体细胞（例如成纤维细胞）重新编程为棕色脂肪细胞。首先，从IPS细胞建立并经过DNA微阵列技术的棕色脂肪细胞中获得mRNA，以找出一些可能在棕色脂肪细胞谱系中具有重要作用的基因。其次，将上述鉴定的一些基因引入了成纤维细胞中，这些基因随后在各种条件下培养。特定基因组合的转染会导致具有多眼脂肪液滴和丰富线粒体的细胞产生。基因的其他一些组合导致了这种细胞的有效产生。细胞的表征强烈建议棕色脂肪细胞的典型特征。有趣的是，与棕色脂肪细胞样细胞相比，基因的某些不同组合诱导的白脂肪细胞样细胞更有效。这些结果强烈建议将成纤维细胞直接重编程为定义的因素。因此，我们目前正在分析直接重编程的最佳条件以及细胞命运决策的分子机制。本研究不仅可能有助于阐明棕色脂肪细胞的分化，而且还有助于产生和表征棕色脂肪细胞的技术。这种技术可能有可能提供新型的再生医学来控制代谢综合征。