Dynamic regulation of genes involved in mitochondrial DNA replication and transcription during mouse brown fat cell differentiation and recruitment.
Dynamic regulation of genes involved in mitochondrial DNA replication and transcription during mouse brown fat cell differentiation and recruitment.
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DOI：
10.1371/journal.pone.0008458
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发表时间：
2009-12-24
期刊：
影响因子：
3.7
通讯作者：
Hansen JB
中科院分区：
文献类型：
--
作者：
Murholm M;Dixen K;Qvortrup K;Hansen LH;Amri EZ;Madsen L;Barbatelli G;Quistorff B;Hansen JB
棕色脂肪细胞专门通过适应性产热来耗散能量，而白色脂肪细胞专门负责能量储存。这些本质上相反的功能可能有两个与线粒体相关的原因，即解偶联蛋白 1 (UCP1) 的表达和棕色脂肪细胞中线粒体丰度显着较高。在这里，我们报告了在体外白色和棕色脂肪细胞分化过程中以及在冷暴露期间白色和棕色脂肪、棕色脂肪组织部分和选定脂肪组织中与线粒体DNA复制、转录和功能相关的基因表达的全面表征。我们发现大多数此类基因在棕色脂肪细胞分化和招募过程中大量诱导，例如脂肪细胞。线粒体转录因子 A (Tfam) 和 B2 (Tfb2m) 的基因，而在白色脂肪转化过程中仅诱导了相同基因的子集。此外，与白色前脂肪细胞和脂肪细胞相比，含有 PR 结构域 16 (PRDM16) 的棕色细胞的表达水平明显更高。我们证明，在棕色脂肪前体细胞中强制表达 Tfam 而不是 Tfb2m 会促进线粒体 DNA 复制，并且在棕色脂肪细胞分化过程中沉默 PRDM16 表达会减弱线粒体生物发生和棕色脂肪细胞标记物的表达。使用白色和棕色脂肪细胞分化的体外和体内模型系统，我们报告了与线粒体生物发生和功能相关的基因表达的详细特征。我们发现白色和棕色脂肪细胞的分化存在显着差异，这可能解释了棕色脂肪转化过程中观察到的线粒体含量显着增加。此外，我们的数据支持 PRDM16 在触发棕色脂肪细胞分化中的关键作用，包括线粒体生物发生和 UCP1 的表达。
Brown adipocytes are specialised in dissipating energy through adaptive thermogenesis, whereas white adipocytes are specialised in energy storage. These essentially opposite functions are possible for two reasons relating to mitochondria, namely expression of uncoupling protein 1 (UCP1) and a remarkably higher mitochondrial abundance in brown adipocytes. Here we report a comprehensive characterisation of gene expression linked to mitochondrial DNA replication, transcription and function during white and brown fat cell differentiation in vitro as well as in white and brown fat, brown adipose tissue fractions and in selected adipose tissues during cold exposure. We find a massive induction of the majority of such genes during brown adipocyte differentiation and recruitment, e.g. of the mitochondrial transcription factors A (Tfam) and B2 (Tfb2m), whereas only a subset of the same genes were induced during white adipose conversion. In addition, PR domain containing 16 (PRDM16) was found to be expressed at substantially higher levels in brown compared to white pre-adipocytes and adipocytes. We demonstrate that forced expression of Tfam but not Tfb2m in brown adipocyte precursor cells promotes mitochondrial DNA replication, and that silencing of PRDM16 expression during brown fat cell differentiation blunts mitochondrial biogenesis and expression of brown fat cell markers. Using both in vitro and in vivo model systems of white and brown fat cell differentiation, we report a detailed characterisation of gene expression linked to mitochondrial biogenesis and function. We find significant differences in differentiating white and brown adipocytes, which might explain the notable increase in mitochondrial content observed during brown adipose conversion. In addition, our data support a key role of PRDM16 in triggering brown adipocyte differentiation, including mitochondrial biogenesis and expression of UCP1.
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影响因子：
3.5
作者：
Ekstrand, MI;Falkenberg, M;Larsson, NG
通讯作者：
Larsson, NG
影响因子：
10.5
作者：
Kajimura, Shingo;Seale, Patrick;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
4.8
作者：
Hansen, JB;Petersen, RK;Kristiansen, K
通讯作者：
Kristiansen, K
DOI：
10.1073/pnas.0611568104
发表时间：
2007-06-19
影响因子：
11.1
作者：
Dali-Youcef, Nassim;Mataki, Chikage;Auwerx, Johan
通讯作者：
Auwerx, Johan
影响因子：
--
作者：
GOGLIA, F;GELOEN, A;BUKOWIECKI, LJ
通讯作者：
BUKOWIECKI, LJ