Multi-Omics Integration Identifies Key Pathways and Regulatory Genes Driving Marbling Formation and Meat Quality in Yunling Cattle

Marbling, or intramuscular fat (IMF), is a primary determinant of high-quality beef, defining key sensory attributes and nutritional value. Yunling (YL) cattle, an indigenous breed from Yunnan, China, are renowned for their superior marbling, yet the underlying molecular mechanisms remain unclear. This study employed an integrated transcriptomic, lipidomic, and amino acid metabolomic approach to systematically compare the multi-omics profiles of the longissimus dorsi muscle among YL, Angus (AGS), and Simmental (XMTE) cattle. Transcriptome analysis identified 2053 and 2156 differentially expressed genes (DEGs) in XMTE vs. YL and AGS vs. YL, respectively. These DEGs were primarily enriched in the PI3K-Akt and MAPK signaling pathways, as well as oxidative phosphorylation. Lipidomic analysis revealed a distinct lipid profile in YL cattle, identifying 27 characteristic lipid molecules (e.g., SM(d20:0/24:1), DG(16:0/18:1(11Z)/0:0)) compared to XMTE and 17 differential lipids compared to AGS. The amino acid metabolome showed that Beta-Alanine and L-Aspartic acid levels in YL were 42.6% and 54.8% lower than in XMTE, respectively (<i>p</i> < 0.01), and levels of several functional amino acids were significantly reduced compared to AGS. Weighted Gene Co-expression Network Analysis (WGCNA) constructed a gene-metabolite network, identifying key modules strongly correlated with lipid and amino acid metabolism (|r| > 0.6). Within these modules, energy metabolism-related genes such as NDUFB1, COX7C, and IDH3B, along with signal transduction genes including ITGB3, PDGFRA, and FN1, were found to synergistically regulate marbling formation in YL cattle. This study systematically elucidates the molecular mechanisms underlying both marbling formation and the nutritional characteristics of meat in Yunling cattle. This provides a theoretical foundation for genetic improvement and offers potential molecular targets to enhance both marbling and overall meat quality in other indigenous cattle breeds worldwide.