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Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis 期刊论文

编号：

55AE6B211C1A6CDD10E8B58648DED7D9
作者：

Lin, Hui#^{[1,2,3,4,5,6]}Ma, Chuanshun#^[7,8]Cai, Kui#^[3,4]Guo, Lulu#^[1,2,9]Wang, Xuemei#^[3,4]Lv, Lin#^[10,11]Zhang, Chao#^[10,11]Lin, Jun#^[3,4]Zhang, Daolai^[12];Ye, Chuan^[3,4];Wang, Tengwei^[1,2];Huang, Shenming^[1,2];Han, Jifei^[7,8];Zhang, Zihao^[7,8];Gao, Junyan^[5,6];Zhang, Mingxiang^[12];Pu, Zhao^[7,8,13];Li, Fengyang^[14];Guo, Yongyuan(郭永园)^[15]Zhou, Xiaojun^[14];Qin, Chengxue^[14];Yi, Fan(易凡)^[16]Yu, Xiao(于晓)*^[7,8]Kong, Wei*^[3,4,17]Jiang, Changtao*^[3,4,18]Sun, JinPeng(孙金鹏)*^{[1,2,3,4,10,11,19]}
语种：

英文
期刊：

SCIENCE ISSN：0036-8075 2025 年 388 卷 6746 期 ; MAY 1
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摘要：

Ceramides play a central role in human health and disease, yet their role as systemic signaling molecules remain poorly understood. In this work, we identify formyl peptide receptor 2 (FPR2) as a membrane receptor that specifically binds long-chain ceramides (C14 to C20). In brown and beige adipocytes, C16:0 ceramide binding to FPR2 inhibits thermogenesis through Gi cyclic adenosine monophosphate signaling pathways, an effect that is reversed in the absence of FPR2. We present three cryo-electron microscopy structures of FPR2 in complex with Gi trimers bound to C16:0, C18:0, and C20:0 ceramides. The hydrophobic tails are deeply embedded in the orthosteric ligand pocket, which has a limited amount of plasticity. Modification of the ceramide binding motif in closely related receptors, such as FPR1 or FPR3, converts them from inactive to active ceramide receptors. Our findings provide a structural basis for adipocyte thermogenesis mediated by FPR2.
推荐引用方式
GB/T 7714：

Lin Hui,Ma Chuanshun,Cai Kui, et al. Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis [J].SCIENCE,2025,388(6746).
APA：

Lin Hui,Ma Chuanshun,Cai Kui,Guo Lulu,&Sun Jin-Peng.(2025).Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis .SCIENCE,388(6746).
MLA：

Lin Hui, et al. "Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis" .SCIENCE 388,6746(2025).
入库时间：

6/4/2025 9:17:21 AM
更新时间：

8/12/2025 9:04:23 AM
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