Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell Metab. 2012 Sep 5;16(3):348-62. doi: 10.1016/j.cmet.2012.08.003.
The developmental origin of adipose tissue and what controls its distribution is poorly understood. By lineage tracing and gene expression analysis in mice, we provide evidence that mesenchymal precursors expressing Myf5--which are thought to give rise only to brown adipocytes and skeletal muscle--also give rise to a subset of white adipocytes. Furthermore, individual brown and white fats contain a mixture of adipocyte progenitor cells derived from Myf5(+) and Myf5(neg) lineages, the number of which varies with depot location. Subsets of white adipocytes originating from both Myf5(+) and Myf5(neg) precursors respond to β(3)-adrenoreceptor stimulation, suggesting "brite" adipocytes may also have multiple origins. We additionally find that deleting PTEN with myf5-cre causes lipomatosis and partial lipodystrophy by selectively expanding the Myf5(+) adipocyte lineages. Thus, the spectrum of adipocytes arising from Myf5(+) precursors is broader than previously thought, and differences in PI3K activity between adipocyte lineages alter body fat distribution.
脂肪组织的发育起源及其分布的调控机制尚不清楚。通过对小鼠的谱系追踪和基因表达分析，我们提供了证据表明，表达 Myf5 的间充质前体细胞——这些细胞被认为仅能分化为棕色脂肪细胞和骨骼肌——也能分化为一部分白色脂肪细胞。此外，个体棕色和白色脂肪中含有源自 Myf5(+)和 Myf5(neg)谱系的混合脂肪祖细胞，其数量随储存部位的不同而变化。源自 Myf5(+)和 Myf5(neg)前体细胞的白色脂肪细胞亚群对β(3)-肾上腺素能受体刺激有反应，表明“米色”脂肪细胞也可能具有多种起源。我们还发现，用 myf5-cre 敲除 PTEN 会通过选择性地扩增 Myf5(+)脂肪细胞谱系，导致脂肪瘤和部分脂肪营养不良。因此，源自 Myf5(+)前体细胞的脂肪细胞谱比以前认为的要广泛，脂肪细胞谱系之间 PI3K 活性的差异会改变体脂肪分布。
