Multi-omics analysis of the regulatory mechanisms of hybridization on intramuscular fat deposition and flavor formation in rabbits

Rabbit meat is a high-quality protein source with low fat and cholesterol content. However, a trade-off exists between growth efficiency and meat quality traits in rabbit production. Reciprocal cross breeding between Rex and Hycole rabbit breeds can integrate complementary genetic advantages. In this study, we employed an integrative multi-omics approach combining transcriptomics, metabolomics, and volatile compound profiling to systematically dissect the genetic and regulatory networks governing muscle growth, intramuscular fat deposition, and flavor formation in reciprocal cross progenies. This study constructed reciprocal cross populations between Rex and Hycole rabbits, including F1 progenies RH (Rex ♂ × Hycole ♀) and HR (Hycole ♂ × Rex ♀) and their derived F2 progenies RHHR (RH ♂ × HR ♀) and HRRH (HR ♂ × RH ♀), and collected samples at 75 and 165 days of age. Multi-omics analyses including transcriptomics, metabolomics, and volatile compound profiling were performed on the longissimus dorsi muscle. Phenotypic evaluation revealed that the RH F1 combination exhibited remarkable heterosis at 75 days, showing higher IMF content, lower drip loss, greater pre-slaughter live weight, and enriched volatile flavor profiles compared with other combinations. In the F2 generation, most growth traits showed heterosis decline, but IMF content did not follow this typical segregation decline pattern, suggesting stable genetic regulation of lipid metabolism. Weighted gene co-expression network analysis and differential expression analysis identified key genes including CALM1 , ME3 , and ASB14 , which coordinately regulate muscle growth, fat deposition, and tenderness through calcium signaling, fatty acid synthesis, and myofiber structure modulation. Metabolomic analysis revealed that MG and eicosa-5,8,11,14-tetraenoic acid ester were positively correlated with IMF content and pre-slaughter live weight. Volatile compound analysis showed upregulation of short-chain alcohols, dipeptides (Val-Leu, Cys-Leu), and the terpenoid Auraptene in the RH75 group, which synergistically enhance meat flavor through the Maillard reaction and lipid oxidation. This study systematically elucidates the molecular mechanisms by which reciprocal cross breeding influences meat quality traits in rabbits. The identified key genes and metabolites provide potential targets for marker-assisted selection and molecular breeding strategies aimed at developing new rabbit varieties with both high growth efficiency and superior meat flavor, thereby promoting sustainable development of the rabbit industry.