Integrated Multiomic Analysis Provides New Insights into the Adipogenic Differentiation of Porcine Adipocytes and Reveals the Regulatory Role of ACACA in Adipogenesis

In this study, the potential regulatory mechanism underlying lipogenesis during porcine preadipocyte differentiation was investigated by integrating multiomic analysis, including transcriptomic, proteomic, and untargeted metabolomic analyses. First, the lipid content in adipocytes on days 0, 4, and 8 of differentiation was detected using Oil Red O staining. Subsequently, the multiomics sequencing of adipocytes at three differentiation stages (D0, D4, and D8) was performed, and the regulatory role of ACACA in adipogenesis was investigated. A total of 5806 differentially expressed genes (DEGs), 875 differentially abundant proteins (DAPs), and 242 differentially abundant metabolites (DAMs) were identified across the three differentiation stages. The DEGs and DAPs identified were involved in PI3K-AKT, PPAR, ECM-receptor interactions, regulation of lipolysis in adipocytes, and focal adhesion pathways, while the DAMs were mainly related to lipolysis in adipocytes and were annotated to pathways related to amino acid metabolism. A total of 273 genes (proteins) were shared between DEGs and DAPs in the D0 vs D4 group, while 274 and 36 genes (proteins) were, respectively, shared between DEGs and DAPs in the D0 vs D8 groups and D4 vs D8 groups. These shared DAPs (DEGs) were mainly enriched in ferroptosis pathway and lipid metabolism-related pathways. Finally, the integration analysis of the three omics indicated that DAPs (DEGs) regulated lipogenesis and porcine preadipocyte differentiation by interacting with DAMs involved in amino acid and fatty acid metabolism. Based on the integrative multiomics analysis results, a crucial DEG (DAP), ACACA, was confirmed to affect adipocyte differentiation and proliferation by regulating fatty acid metabolism. This study provides the opportunity to improve the meat production performance in pigs.