Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis
DOI:
10.1126/science.ado4188
Publication Date:
2025-03-13T17:59:12Z
AUTHORS (26)
ABSTRACT
Ceramides play a central role in human health and disease, yet their as systemic signaling molecules remain poorly understood. In this work, we identify FPR2 membrane receptor that specifically binds long-chain ceramides (C14-C20). brown beige adipocytes, C16:0 ceramide binding to inhibits thermogenesis via G i -cyclic AMP pathways, an effect is reversed the absence of FPR2. We present three cryo–electron microscopy structures complex with trimers bound C16:0, C18:0 C20:0 ceramides. The hydrophobic tails are deeply embedded orthosteric ligand pocket, which has limited amount plasticity. Modification motif closely related receptors, such FPR1 or FPR3, converts them from inactive active receptors. Our findings provide structural basis for adipocyte mediated by
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