Myostatin inhibits brown adipocyte differentiation via regulation of Smad3-mediated β-catenin stabilization
Myostatin inhibits brown adipocyte differentiation via regulation of Smad3-mediated β-catenin stabilization
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DOI：
10.1016/j.biocel.2011.11.004
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发表时间：
2012-02-01
影响因子：
4
通讯作者：
Lee, Sang Chul
中科院分区：
文献类型：
--
作者：
Kim, Won Kon;Choi, Hye-Ryung;Lee, Sang Chul
棕色脂肪细胞在调节能量平衡中起着重要的作用，肥胖与棕色脂肪组织的数量有很好的相关性。虽然白色脂肪细胞分化的分子机制已被很好地表征，但棕色脂肪的形成尚未得到广泛的研究。此外，调节棕色脂肪形成分化的细胞外因子尚未完全了解。在这里，我们利用原代棕色前脂肪细胞评估了肌生长抑制素在棕色脂肪形成分化中的调节作用机制。我们的研究结果清楚地表明，肌肉生长抑制素治疗可以显著抑制棕色脂肪细胞的分化。此外，在分化早期观察到肌生成抑制素诱导的褐色脂肪生成的抑制。肌生长抑制素诱导Smad3磷酸化，导致β -连环蛋白稳定性增加。这些作用被Smad3抑制剂阻断。棕色脂肪细胞相关基因，如ppar - γ、UCP-1、PGC-1 α和PRDM16的表达在肌生长抑制素治疗后显著下调，并在与β -连环蛋白激活剂共同治疗时进一步下调。综上所述，目前的研究表明，肌肉生长抑制素是一种有效的负调节因子，通过调节smad3诱导的β -连环蛋白稳定，棕色脂肪形成分化。我们的研究结果表明，肌生长抑制素可能被用作控制棕色脂肪细胞分化的细胞外因子。(C) 2011 Elsevier Ltd.版权所有。
Brown adipocytes play an important role in regulating energy balance, and there is a good correlation between obesity and the amount of brown adipose tissue. Although the molecular mechanism of white adipocyte differentiation has been well characterized, brown adipogenesis has not been studied extensively. Moreover, extracellular factors that regulate brown adipogenic differentiation are not fully understood. Here, we assessed the mechanism of the regulatory action of myostatin in brown adipogenic differentiation using primary brown preadipocytes. Our results clearly showed that differentiation of brown adipocytes was significantly inhibited by myostatin treatment. In addition, myostatin-induced suppression of brown adipogenesis was observed during the early phase of differentiation. Myostatin induced the phosphorylation of Smad3, which led to increased beta-catenin stabilization. These effects were blocked by treatment with a Smad3 inhibitor. Expression of brown adipocyte-related genes, such as PPAR-gamma, UCP-1, PGC-1 alpha, and PRDM16, were dramatically down-regulated by treatment with myostatin, and further down-regulated by co-treatment with a beta-catenin activator. Taken together, the present study demonstrated that myostatin is a potent negative regulator of brown adipogenic differentiation by modulation of Smad3-induced beta-catenin stabilization. Our findings suggest that myostatin could be used as an extracellular factor in the control of brown adipocyte differentiation. (C) 2011 Elsevier Ltd. All rights reserved.