Chronic Peroxisome Proliferator-activated Receptor γ (PPARγ) Activation of Epididymally Derived White Adipocyte Cultures Reveals a Population of Thermogenically Competent, UCP1-containing Adipocytes Molecularly Distinct from Classic Brown Adipocytes
Chronic Peroxisome Proliferator-activated Receptor γ (PPARγ) Activation of Epididymally Derived White Adipocyte Cultures Reveals a Population of Thermogenically Competent, UCP1-containing Adipocytes Molecularly Distinct from Classic Brown Adipocytes
复制标题
DOI：
10.1074/jbc.m109.053942
复制
发表时间：
2010-03-05
影响因子：
4.8
通讯作者：
Nedergaard, Jan
中科院分区：
文献类型：
--
作者：
Petrovic, Natasa;Walden, Tomas B.;Nedergaard, Jan
最近的见解，棕色脂肪细胞和肌肉细胞共享一个共同的起源，并在这方面是不同于白色脂肪细胞已经引发了有关的起源和分子特征的问题，在经典的白色脂肪组织仓库在某些生理或药理条件下观察到的UCP 1表达细胞。检查前体从最纯的白色脂肪组织仓库（附睾），我们在这里报告，慢性治疗与过氧化物酶体增殖物激活受体γ激动剂罗格列酮不仅促进PGC-1 α的表达和在这些细胞中的增殖，但也去甲肾上腺素增强UCP 1基因表达的一个重要的细胞亚群，提供这些细胞与真正的产热能力。然而，尽管功能性产热基因表达，但细胞缺乏与经典棕色脂肪细胞相关的新型转录因子（Zic 1、Lhx 8、Meox 2和特征性PRDM 16）或肌细胞相关基因（肌细胞生成素和myomir（肌肉特异性microRNA））的转录物，并保留了白色脂肪特征，如Hoxc 9表达。共培养实验证实，表达UCP 1的细胞不是增殖的经典棕色脂肪细胞（脂肪肌细胞），因此这些细胞构成了具有发育起源和分子特征的脂肪细胞亚群（“brite”脂肪细胞），将它们区分为单独的细胞类别。
The recent insight that brown adipocytes and muscle cells share a common origin and in this respect are distinct from white adipocytes has spurred questions concerning the origin and molecular characteristics of the UCP1-expressing cells observed in classic white adipose tissue depots under certain physiological or pharmacological conditions. Examining precursors from the purest white adipose tissue depot (epididymal), we report here that chronic treatment with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone promotes not only the expression of PGC-1 alpha and mitochondriogenesis in these cells but also a norepinephrine-augmentable UCP1 gene expression in a significant subset of the cells, providing these cells with a genuine thermogenic capacity. However, although functional thermogenic genes are expressed, the cells are devoid of transcripts for the novel transcription factors now associated with classic brown adipocytes (Zic1, Lhx8, Meox2, and characteristically PRDM16) or for myocyte-associated genes (myogenin and myomirs (muscle-specific microRNAs)) and retain white fat characteristics such as Hoxc9 expression. Co-culture experiments verify that the UCP1-expressing cells are not proliferating classic brown adipocytes (adipomyocytes), and these cells therefore constitute a subset of adipocytes ("brite" adipocytes) with a developmental origin and molecular characteristics distinguishing them as a separate class of cells.