Unraveling the molecular basis of aggression in pigs through integrated transcriptomic and metabolomic analyses

In commercial pig production, weaned piglets exhibit more aggressive behavior after mixing, which adversely affects animal welfare and pig performance. This study integrated metabolomics and transcriptomics to assess the characterization of the hypothalamus and pituitary gland in pigs with differing aggression levels. We identified metabolite markers, including Fa 18:2+2o, Flonicamid, Ionomycin, Pyridine, Diacetyl, and γ-aminobutyric acid (GABA), associated with the most aggressive behavior in pigs. Transcriptomic analysis revealed 1,204 and 643 differentially expressed genes (DEGs) in the hypothalamus and pituitary gland, respectively. Pathway analysis linked the DEMs and DEGs to the 'GABAergic synapse', suggesting its involvement in aggression. We constructed a regulatory network from the sequencing data, incorporating GABA-related genes, transcription factors, and metabolites. Key transcription factors, including <italic>ELK1</italic>, <italic>STAT3</italic>, <italic>SOX17</italic>, and <italic>SRF</italic>, may regulate GABA metabolism and influence aggressive behavior. Our findings highlight GABA metabolism's role in aggression regulation and offer insights into its neurobiological underpinnings and molecular mechanisms.