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BMP4 facilitates beige fat biogenesis via regulating adipose tissue macrophages Free
Shu-Wen Qian , Meng-Yuan Wu, Yi-Na Wang, Ya-Xin Zhao, Ying Zou, Jia-Bao Pan, Yan Tang, Yang Liu, Liang Guo, and Qi-Qun Tang *
Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China
These authors contributed equally to this work.
*Correspondence to:Qi-Qun Tang, E-mail: qqtang@shmu.edu.cn
J Mol Cell Biol, Volume 11, Issue 1, January 2019, Pages 14-25  https://doi.org/10.1093/jmcb/mjy011
Keyword: BMP4, fat browning, adipose tissue macrophages

Thermogenic beige fat improves metabolism and prevents obesity. Emerging evidence shows that the activation of M2 macrophages stimulates beige adipogenesis, whereas the activation of M1 macrophages, which play a major role in inflammation, impedes beige adipogenesis. Thus, the identification of factors that regulate adipose tissue macrophages (ATMs) will help clarify the mechanism involved in beiging. Here, we found that one of the secreted proteins in adipose tissue, namely, BMP4, alters the ATM profile in subcutaneous adipose tissue by activating M2 and inhibiting M1 macrophages. Mechanistically, the BMP4-stimulated p38/MAPK/STAT6/PI3K–AKT signalling pathway is involved. Meanwhile, BMP4 improved the potency of M2 macrophages to induce beige fat biogenesis. Considering that the overexpression of BMP4 in adipose tissue promotes the beiging of subcutaneous adipose tissue and improves insulin sensitivity, these findings provide evidence that BMP4 acts as an activator of beige fat by targeting immuno-metabolic pathways.