Breaking the code of pig aggression: GABA identified as key regulator

Researchers identified key metabolites and differentially expressed genes in the hypothalamus and pituitary gland of pigs with varying aggression levels. Notably, pathways involving γ-aminobutyric acid (GABA) were consistently enriched, suggesting a central role in modulating aggression. A regulatory network involving GABA-related genes, transcription factors, and metabolites was constructed, highlighting ELK1, STAT3, SOX17, and SRF as key transcriptional regulators.

Aggression is a fundamental evolutionary behavior that helps animals secure resources, establish dominance, and survive. However, in commercial pig production, mixing unfamiliar piglets often triggers excessive aggression, leading to injuries, stress, and compromised meat quality. Previous research has highlighted the hypothalamic-pituitary-adrenal (HPA) axis and neurotransmitters like serotonin and dopamine in aggression regulation. While genetic studies have associated certain genes with aggression in animals, the exact neurobiological and metabolic mechanisms remain elusive. Metabolites, which reflect both genetic and environmental influences, have emerged as promising markers in behavioral studies. Based on these challenges, there is a pressing need to explore the integrative roles of genes and metabolites in aggression to develop effective mitigation strategies.

A study (DOI: 10.48130/animadv-0025-0015) published in Animal Advances on 25 June 2025 by Bo Zhou’s team, Nanjing Agricultural University, provides novel molecular insights and open pathways to mitigate aggression in animals through neurochemical intervention.

In this study, researchers employed untargeted metabolomics using liquid chromatography–mass spectrometry (LC-MS) to examine metabolic variations in the hypothalamus (HP) and pituitary gland (PG) of pigs displaying contrasting levels of aggressive behavior.  Principal component analysis (PCA) revealed distinct clustering between brain regions and aggression groups, highlighting significant divergence in metabolite profiles. A total of 1,234 metabolites were detected, with 877 annotated, among which lipids and organic acids were the most abundant classes. Clustering methods (Mfuzz and K-means) identified key metabolite groups exhibiting differential expression between high (HPM/PGM) and low (HPL/PGL) aggression pigs. Further statistical screening identified 67 and 56 differentially expressed metabolites (DEMs) in the HP and PG, respectively. Combining clustering and DEM analyses, 15 and 14 candidate biomarkers were identified for low and high aggression phenotypes, respectively. Several of these, including GABA, corticosterone, and pyruvaldehyde, demonstrated high diagnostic potential with area under the ROC curve (AUC) scores exceeding 0.875. Functional enrichment and WGCNA revealed that metabolites associated with aggression were significantly involved in neurochemical signaling pathways such as the GABAergic synapse, synaptic vesicle cycle, and cAMP signaling. Notably, corticosterone levels were significantly elevated in aggressive pigs, aligning with the involvement of the HPA axis. This integrative approach underscored the pivotal role of GABA metabolism and related pathways in modulating aggression, establishing a molecular foundation for future behavioral and therapeutic interventions.

These findings hold significant potential for improving livestock management.  By targeting GABA metabolism—either through dietary supplements or genetic selection—farmers may reduce pig aggression, minimize injuries, and enhance productivity. Beyond animal agriculture, the study deepens our understanding of aggression’s molecular roots, with implications for psychiatric research. As GABA also influences human mood and stress response, the identified regulatory mechanisms could inform treatment development for behavioral disorders.

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References

DOI

10.48130/animadv-0025-0015

Original Source URL

https://doi.org/10.48130/animadv-0025-0015

Funding information

This work was supported by the National Natural Science Foundation of China (Grant No. 32172786), the Independent Innovation Funds for Agricultural Science and Technology in Jiangsu Province [CX(24)1014], and the 'JBGS' Project of Breeding Industry Revitalization in Jiangsu Province (JBGS[2021]101).

About Animal Advances

Animal Advances is an open-access journal which published by Maximum Academic Press in partnership with Nanjing Agricultural University. The journal is dedicated to delivering cutting-edge discoveries and progress in animal sciences to a diverse audience, encompassing scholars, academicians, and practitioners in the industry.