Bone morphogenetic protein-11 (BMP11), also known as growth differentiation factor-11 (GDF11), is implicated in skeletal development and joint morphogenesis in mammals. However, its functions in adipogenesis and energy homeostasis are mostly unknown. The present study investigates crucial roles of BMP11 in cultured 3T3-L1 white and HIB1B brown adipocytes, using Bmp11 gene depletion and pharmacological inhibition of BMP11. The silencing of Bmp11 markedly decreases the expression levels of brown-fat signature proteins and beige-specific genes in white adipocytes and significantly down-regulates the expression levels of brown fat-specific genes in brown adipocytes. The deficiency of Bmp11 reduces the expressions of lipolytic protein markers in white and brown adipocytes. Moreover, BMP11 induces browning of 3T3-L1 adipocytes via coordination of multiple signalling pathways, including mTORC1-COX2 and p38MAPK-PGC-1α as non-canonical pathways, as well as Smad1/5/8 as a canonical pathway. We believe this study is the first to provide evidence of the potential roles of BMP11 for improvement of lipid catabolism in both cultured white and brown adipocytes, as well as the effect on browning of white adipocytes. Taken together, these results demonstrate the therapeutic potential for the treatment of obesity.

中文翻译：

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BMP11 调节白色和棕色脂肪细胞的产热

骨形态发生蛋白 11 (BMP11)，也称为生长分化因子 11 (GDF11)，与哺乳动物的骨骼发育和关节形态发生有关。然而，它在脂肪生成和能量稳态中的功能大多是未知的。本研究使用Bmp11基因耗竭和 BMP11 的药理学抑制，研究了 BMP11 在培养的 3T3-L1 白色和 HIB1B 棕色脂肪细胞中的关键作用。Bmp11的沉默显着降低了白色脂肪细胞中棕色脂肪特征蛋白和米色特异性基因的表达水平，并显着下调棕色脂肪细胞中棕色脂肪特异性基因的表达水平。Bmp11的缺陷降低白色和棕色脂肪细胞中脂解蛋白标志物的表达。此外，BMP11 通过协调多种信号通路，包括 mTORC1-COX2 和 p38MAPK-PGC-1α 作为非规范通路，以及作为规范通路的 Smad1/5/8，诱导 3T3-L1 脂肪细胞褐变。我们相信这项研究首次提供了 BMP11 在改善培养的白色和棕色脂肪细胞中脂质分解代谢方面的潜在作用的证据，以及对白色脂肪细胞褐变的影响。总之，这些结果证明了治疗肥胖症的治疗潜力。