In conclusion, we identified PPARα as a direct target of FMN, and our data firstly indicated that FMN ameliorates LPS-induced depression-like behaviors through rebalancing microglia M1/M2 polarization and inhibiting NLRP3 inflammasome, with involvement of activating PPARα-mediated autophagy (Fig. 9). Here, PPARA is linked to major depressive disorder.