Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages
Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages
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DOI：
10.1073/pnas.0610615104
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发表时间：
2007-03-13
影响因子：
11.1
通讯作者：
Cannon, Barbara
中科院分区：
文献类型：
--
作者：
Timmons, James A.;Wennmalm, Kristian;Cannon, Barbara
在白色脂肪细胞中获得棕色脂肪细胞表型，具有丰富的线粒体和增加的能量消耗潜力，是对抗肥胖的合理策略。原代棕色脂肪细胞表型的独特转录调节因子尚不清楚，这限制了我们促进棕色脂肪形成而非白色脂肪的能力。在目前的工作中，我们使用微阵列分析策略来研究原代前脂肪细胞，我们做出了惊人的发现，棕色前脂肪细胞表现出肌源性转录特征，而棕色和白色原代前脂肪细胞表现出与永生化脂肪形成模型中发现的特征不同的特征。我们在棕色脂肪细胞分化过程中发现了一个看似合理的 SIRT1 相关转录特征，这可能有助于沉默肌源性特征。与棕色前脂肪细胞或骨骼肌细胞相反，白色前脂肪细胞表达 Tcf21，这是一种转录因子，已被证明可以抑制肌生成和核受体活性。此外，我们还发现了一些在棕色和白色前脂肪细胞之间差异表达的发育基因，并且最近与人类肥胖有关。肌细胞和棕色前脂肪细胞之间的相互联系证实了棕色脂肪组织与白色脂肪组织的不同起源，并且也代表了为什么棕色脂肪细胞最终专门从事脂质分解代谢而不是储存的合理解释，就像氧化骨骼肌组织一样。
Attainment of a brown adipocyte cell phenotype in white adipocytes, with their abundant mitochondria and increased energy expenditure potential, is a legitimate strategy for combating obesity. The unique transcriptional regulators of the primary brown adipocyte phenotype are unknown, limiting our ability to promote brown adipogenesis over white. In the present work, we used microarray analysis strategies to study primary preadipocytes, and we made the striking discovery that brown preadipocytes demonstrate a myogenic transcriptional signature, whereas both brown and white primary preadipocytes demonstrate signatures distinct from those found in immortalized adipogenic models. We found a plausible SIRT1-related transcriptional signature during brown adipocyte differentiation that may contribute to silencing the myogenic signature. In contrast to brown preadipocytes or skeletal muscle cells, white preadipocytes express Tcf21, a transcription factor that has been shown to suppress myogenesis and nuclear receptor activity. In addition, we identified a number of developmental genes that are differentially expressed between brown and white preadipocytes and that have recently been implicated in human obesity. The interlinkage between the myocyte and the brown preadipocyte confirms the distinct origin for brown versus white adipose tissue and also represents a plausible explanation as to why brown adipocytes ultimately specialize in lipid catabolism rather than storage, much like oxidative skeletal muscle tissue.