Sanchez-Gurmaches Joan, Guertin David A
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, Massachusetts 01605, USA.
Nat Commun. 2014 Jun 19;5:4099. doi: 10.1038/ncomms5099.
Adipose tissue development is poorly understood. Here we use a lineage-tracing strategy optimal for adipocytes to provide evidence that Myf5 precursors are not the exclusive source of brown adipocytes and contribute more to the mature white and brite adipocyte populations than previously thought. Moreover, Myf5-lineage distribution in adipose tissue changes in response to modifiable and non-modifiable factors. We also find that the Pax3 lineage largely overlaps with the Myf5 lineage in brown fat and subcutaneous white fat, but exhibits gender-linked divergence in visceral white fat while the MyoD1 lineage does not give rise to any adipocytes. Finally, by deleting insulin receptor beta in the Myf5 lineage, we provide in vivo evidence that the insulin receptor is essential for adipogenesis and that adipocyte lineages have plasticity. These data establish a conceptual framework for adipose tissue development and could explain body fat patterning variations in healthy and lipodystrophic or obese humans.
脂肪组织的发育目前了解甚少。在此，我们采用了一种对脂肪细胞最为适用的谱系追踪策略，以提供证据表明，Myf5前体细胞并非棕色脂肪细胞的唯一来源，并且其对成熟白色脂肪细胞和米色脂肪细胞群体的贡献比之前认为的更多。此外，脂肪组织中Myf5谱系的分布会因可改变和不可改变的因素而发生变化。我们还发现，Pax3谱系在棕色脂肪和皮下白色脂肪中与Myf5谱系在很大程度上重叠，但在内脏白色脂肪中表现出与性别相关的差异，而MyoD1谱系不会产生任何脂肪细胞。最后，通过在Myf5谱系中删除胰岛素受体β，我们提供了体内证据，证明胰岛素受体对脂肪生成至关重要，并且脂肪细胞谱系具有可塑性。这些数据为脂肪组织发育建立了一个概念框架，并且可以解释健康人群以及脂肪营养不良或肥胖人群体内脂肪分布模式的差异。
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