Multi-tissue transcriptomic atlas reveals systemic effects of FGF19 on metabolism and immunity

Fibroblast growth factor 19 (FGF19) signaling is a promising therapeutic target for metabolic diseases and cancers, and several agents targeting the FGF19 signaling are currently undergoing clinical trials. However, as an endocrine FGF, FGF19's organism-wide functions remain vague, which hinders the advancing of FGF19 signaling-based therapies. To systematically explore its systemic effects, we performed a multi-tissue transcriptomic profiling in a FGF19 knock-in mouse model. Sustained FGF19 exposure induced extensive, tissue‑specific transcriptional reprogramming. For instance, lipid metabolic pathways were broadly altered not only in canonical metabolic organs but also in immune‑related tissues including the spleen and thymus. Furthermore, integrated analysis and functional validation demonstrated that FGF19 promoted monocyte/macrophage (Mo/MΦ) migration in an FGFR4‑involved manner, associated with an M2-like polarization state. Moreover, we developed a macrophage‑targeted sustained‑release FGF19 delivery system, which significantly accelerated wound healing and enhanced M2 macrophage infiltration in a murine full‑thickness skin injury model. Overall, our study establishes a multi‑tissue transcriptional atlas of FGF19 action, reveals broad metabolic and immune regulatory responses to sustained human FGF19 exposure in mice, and provides a targeted therapeutic strategy for modulating macrophage.