BMP-9 as a potent brown adipogenic inducer with anti-obesity capacity
BMP-9 as a potent brown adipogenic inducer with anti-obesity capacity
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DOI：
10.1016/j.biomaterials.2013.12.063
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发表时间：
2014-03-01
期刊：
影响因子：
14
通讯作者：
Lee, Dong Kun
中科院分区：
文献类型：
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作者：
Kuo, Mario Meng-Chiang;Kim, Sooho;Lee, Dong Kun
BMP-9在肝细胞中表达最高，已被证明可调节参与葡萄糖稳态的酶的表达。然而，这种影响的潜在机制尚未阐明。我们观察到，MB109，一种重组BMP-9衍生物，增强了人脂肪组织来源的干细胞的棕色脂肪生成。通过对细胞培养系统的观察，我们假设MB109可能能够通过调节棕色脂肪形成基因的表达来改善葡萄糖代谢。全身性腹膜内注射MB109（200 μ g/kg/wk）通过减小白色脂肪细胞的大小和降低16小时空腹血糖水平而抑制高脂饮食诱导的肥胖小鼠的体重增加，而不改变食物消耗或明显的行为表现。MB109诱导棕色脂肪形成基因在皮下而不是在内脏脂肪组织中的表达。此外，全身注射MB109增强了肥胖小鼠肝脏中脂肪酸合成酶的表达，这可能有助于减轻肥胖相关的血糖水平升高。我们的研究结果表明BMP-9在棕色脂肪形成和抑制高脂饮食诱导的肥胖症的病理生理学中的作用，推测是通过激活素受体样激酶1信号通路。(C)2013爱思唯尔有限公司版权所有。
BMP-9, whose expression is highest in liver cells, has been demonstrated to regulate expression of enzymes involved in glucose homeostasis. However, the underlying mechanism of this effect has yet to be elucidated. We observed that MB109, a recombinant BMP-9 derivative, enhanced brown adipogenesis of human adipose tissue derived stem cells. With this observation of the cell culture system, we hypothesized that MB109 may be able to improve glucose metabolism by regulating expression of brown adipogenic genes. Systemic intraperitoneal injection of MB109 (200 mu g/kg/wk) suppressed weight gaining of high fat diet-induced obese mice by reducing sizes of white adipocytes and decreased 16 h fasting blood glucose levels without changing food consumption or apparent behavioral performances. MB109 induced expression of brown adipogenic genes in the subcutaneous but not in the visceral fat tissues from the mice fed with high fat diet. In addition, systematic injection of MB109 enhanced fatty acid synthase expression in the liver of obese mice, which may help attenuate an obesity-associated increase of blood glucose levels. Our results demonstrate a role of BMP-9 in brown adipogenesis and suppressing pathophysiology of high fat diet-induced obesity, presumably through the activin receptor like kinase 1 signaling pathway. (C) 2013 Elsevier Ltd. All rights reserved.