BMP11 regulates thermogenesis in white and brown adipocytes

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-1 alpha 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.

Automated summary

This study demonstrates the important roles of BMP11 in white and brown adipocytes, showing that silencing of Bmp11 affects the expression of specific genes and reduces the levels of lipolytic protein markers. Moreover, BMP11 induces browning of 3T3-L1 adipocytes by coordinating multiple signaling pathways, including mTORC1-COX2 and p38MAPK-PGC-1 alpha as non-canonical pathways, as well as Smad1/5/8 as a canonical pathway. These results suggest the therapeutic potential of BMP11 for obesity treatment.