MicroRNA-375-3p Targets Fatty Acid Synthase and Relish to Regulate Energy Allocation During Pupal Metamorphosis and Starvation

Energy reallocation is critical for organismal survival under developmental transitions and nutrient restriction. However, whether developmentally and nutritionally induced energy deficiency are governed by convergent regulatory mechanisms remains poorly understood. Here, we identify miR-375-3p as a central regulator that coordinates energy use during both pupal metamorphosis and starvation using the Tribolium castaneum. Upregulated by endocrine cues including 20-hydroxyecdysone and insulin, miR-375-3p redirects energy by suppressing de novo lipogenesis through fatty acid synthase (FASN) and enhancing lipolysis via Relish inhibition. This regulatory shift mobilizes stored reserves while suppressing energetically costly immune and oxidative responses, thereby prioritizing energy supply to the central nervous system. Under fed conditions, miR-375-3p levels decline, restoring energy distribution across all tissues and enabling immune competence. These findings reveal a conserved miRNA-centered mechanism that mediates metabolic adaptation to energy scarcity and provide new insights into miRNA-driven control of energy balance.