Integrated Multi-omics Analysis Identifies Key Genes and Metabolites Regulating Ovine Adipogenesis

Background Adipocytes direct carbon substrates, including glucose and glutamate, into diverse metabolic pathways, in which energy is ultimately stored as triglycerides within lipid droplets. However, excessive tail fat deposition not only reduces economic efficiency but also hinders natural mating, forming a key constraint in Guangling large-tailed sheep. Results In this study, stromal vascular fraction cells (SVF) derived from Guangling large-tailed sheep were subjected to a 7-day in vitro adipogenic differentiation. These differentiated adipocytes (DA) accumulated substantially more lipids and lipid droplets than SVF. Only differentiated adipocytes showed a higher ROS level compared to other cells. Comparative omics analysis identified 1,581 differentially expressed genes (DEGs) and 14 differentially accumulated metabolites (DAMs) in the SVF and DA. Co-joint analysis revealed membrane phospholipids remodeling is enhanced by the upregulation of PLA2G6, LPCAT3 and LPGAT1, thereby maintaining the unsaturation level of membrane phospholipids. Glutathione specifically eliminates reactive carbonyl species generated from lipid peroxidation through upregulated MGST1, providing a plausible explanation for the high unsaturation level of phospholipids. Conclusions This study identifies PLA2G6, LPCAT3, LPGAT1, and MGST1 as key genes regulating phospholipid remodeling and oxidative defense during fat deposition, and offers actionable targets for marker‑assisted selection of precision livestock farming.