Integrated proteomics and metabolomics elucidate HSD17B12 regulation of intramuscular fat deposition for enhanced beef quality

Intramuscular fat (IMF) critically governs beef sensory attributes (juiciness, tenderness, flavor). Previous studies have predominantly focused on genomics and transcriptomics, with limited proteomic data available. To gain a more comprehensive understanding of the mechanisms regulating IMF deposition, we integrated proteomic and metabolomic profiling of the Longissimus dorsi across three genetically distinct cattle breeds. A comprehensive analysis of 633 differentially abundant proteins (DAPs) and 1456 differential metabolites (DAMs) identified 20 potential protein regulators (e.g., ACAA1, ACACA, ADIPOQ, and HSD17B12) and 19 candidate metabolites (e.g., hexadecanoic acid, icosadienoic acid, oleic acid, and oxaloacetate) as key molecular markers. Furthermore, HSD17B12 was found to inhibit IMF cell proliferation while promoting differentiation and lipid accumulation. This integrated approach highlights HSD17B12 as a critical regulator in enhancing IMF content, providing a theoretical foundation for improving beef quality. • Integrated DIA-PRM proteomics and metabolomics to analyze IMF deposition in cattle. • Identified 20 proteins and 19 metabolites as biomarkers for IMF traits. • Targeting HSD17B12 was demonstrated as a strategy to improve beef quality.