Interleukin-27 (IL-27) is involved in obesity progression, but the regulatory mechanisms underlying IL-27 production in obesity-related inflammation remain unclear. Glucagon-like peptide-1 (GLP-1) modulates macrophage polarization and inflammatory gene expression. This study explored whether GLP-1 induces IL-27 synthesis in RAW264.7 macrophages and mouse peritoneal macrophages. Cells were treated with GLP-1 alone or combined with Exendin (9-39) or PI3K inhibitors for 24 h. IL-27 levels were measured by enzyme-linked immunosorbent assay (ELISA), RT-qPCR, and Western blotting; macrophage polarization was analyzed by RT-qPCR. We found that GLP-1 promoted IL-27 expression in a dose- and time-dependent manner via the PI3K/AKT signaling pathway. Under basal conditions, IL-27 promoted macrophage polarization toward an M1 phenotype and increased proinflammatory cytokine expression; in contrast, IL-27 suppressed proinflammatory cytokine expression under inflammatory conditions. In conclusion, GLP-1 induces IL-27 production in RAW264.7 macrophages and mouse peritoneal macrophages through PI3K/AKT activation. IL-27 displays context-dependent inflammatory functions, which may provide new insights into obesity-associated immune regulation.
