GREM2 is associated with human central obesity and inhibits visceral preadipocyte browning
Wen Liu, Danjie Li, Minglan Yang, Long Wang, Yu Xu, Na Chen, Zhiyin Zhang, Juan Shi, Wen Li, Shaoqian Zhao, Aibo Gao, Yufei Chen, Qinyun Ma, Ruizhi Zheng, Shujing Wu, Yifei Zhang, Yuhong Chen, Shuwen Qian, Yufang Bi, Weiqiong Gu, Qi‐Qun Tang, Guang Ning, Ruixin Liu, Weiqing Wang, Jie Hong, Jiqiu Wang
Abstract
BACKGROUND: Some circulating proteins are linked to central adiposity. Gremlin 2 (GREM2) functions as a secreted factor involved in osteogenesis and adipogenesis. Here, we investigated the association of blood GREM2 levels and central adiposity, and the biological roles of GREM2 in the browning program of visceral preadipocytes. METHODS: Three independent cohorts were applied to detect circulating GREM2 levels. Recombinant Grem2 protein, Grem2 overexpression and knockout mouse models, and preadipocyte-specific Bmpr2 knockout mice were used to assess the roles of Grem2 in the browning program. FINDINGS: preadipocytes abolished the antagonistic effect of Grem2. INTERPRETATION: These findings indicate that GREM2 might function as a circulating protein factor associated with human visceral adiposity, and Grem2 inhibits the browning capacity of visceral preadipocytes partially by BMP4/7-BMPR2 signaling pathway. FUNDING: The complete list of funders can be found in the Acknowledgement section.