Integrated Transcriptomics and Metabolomics Unveil Key Regulators of Feed Efficiency in <i>Larimichthys crocea</i> on Fishmeal‐Free Diets

Understanding the molecular underpinnings of feed efficiency (FE) is crucial for advancing sustainable aquaculture, particularly under fishmeal‐free (FM‐free) dietary strategies. This study investigated the physiological, transcriptomic, and metabolomic differences between high‐FE and low‐FE Larimichthys crocea individuals fed a plant‐based diet. High‐FE fish exhibited significantly higher activities of hepatic amylase (AMS), hepatic lipase (HL), and lipoprotein lipase (LPL), as well as changed serum albumin (ALB) and peroxidase (POD) levels, suggesting enhanced digestive function and antioxidant capacity. Transcriptomic analysis revealed 239 differentially expressed genes (DEGs), with significant enrichment in steroid biosynthesis, ribosome biogenesis, and autophagy pathways. Genes involved in glycolysis were downregulated, indicating a metabolic shift toward increased reliance on lipid and protein catabolism. Metabolomic profiling identified 359 differentially expressed metabolites (DEMs), primarily comprising lipids and amino acids, enriched in pathways related to amino acid metabolism, energy production, and ABC transporter activity. Integrative O2PLS and correlation analyses identified tightly linked gene–metabolite pairs, such as pfkp and peptide fragment, and highlighted mao as a regulatory factor that links energy and protein digestion. Protein–protein interaction (PPI) analysis identified five hub genes ( tpi1 , tktl2 , fdps , pgam1 , and ldha ) that are central to metabolic coordination. These findings offer comprehensive insights into the metabolic reprograming and regulatory mechanisms underlying enhanced FE in L. crocea , highlighting potential molecular targets for selective breeding and feed optimization in FM‐free aquaculture systems.