Transcriptomic and proteomic insights into the growth-promoting mechanisms of dietary γ-aminobutyric acid (GABA) in tawny puffer (Takifugu flavidus)

γ-aminobutyric acid (GABA) has been shown to promote growth in certain aquatic species, yet the molecular mechanisms remain unclear. This study investigated the effects of GABA in juvenile tawny puffer (Takifugu flavidus) via growth performance, liver transcriptomic and proteomic analyses, and plasma stress indices. Dietary supplementation with 100 mg/kg GABA for 50 days significantly improved weight gain rate (WGR) and specific growth rate (SGR), alongside higher feeding rate (FR) and hepatosomatic index (HSI). Transcriptomic profiling identified DEGs predominantly enriched in growth-related signal pathways (MAPK, TGF-β), and anabolic processes: lipid metabolism (fatty acid elongation, fatty-acyl-CoA and fatty acid derivative biosynthetic), nucleic acid synthesis (nucleotide, purine), and nutrient metabolism (vitamin B6, tryptophan). Proteomic analysis revealed DEPs primarily enriched in regulatory processes: nitrogen metabolism, nicotinate/nicotinamide metabolism, and arachidonic acid metabolism. Both omics datasets confirmed GABA's stress mitigation—transcriptomic downregulation of stress pathways (cortisol synthesis, oxytocin signaling, Cushing syndrome) and proteomic enrichment of neuroactive ligand-receptor interactions, validated by lower plasma stress indices in the GABA group. PPI analysis revealed that GABA promotes growth in T. flavidus by activating growth-related proteins [e.g., Actin, alpha skeletal muscle A (ACTA1B)], inhibiting ubiquitin-like protein 7B (UBL7B), and coordinating four growth and development functional subnetworks. In conclusion, GABA promotes the growth of T. flavidus by activating growth-related signal pathways and anabolic/regulatory metabolism, mitigating stress, and regulating growth-related and ubiquitin-like proteins. This is the first study to unravel GABA's liver-mediated growth-promoting mechanisms in T. flavidus via comprehensive approaches, providing a basis for developing GABA as a functional feed additive.