Tissue-specific metabolic remodeling to opposite fatty acid oxidation regulation in golden pompano identified by dual-tissue multi-omics

High-protein feeding is widely used in carnivorous marine fish to sustain growth, but it increases dependence on costly fishmeal. In practice, protein sparing by increasing dietary lipid levels leads to inconsistent results, as lipid utilization is limited by mitochondrial fatty acid oxidation (FAO) capacity, potentially inducing adiposity instead of growth. Here, golden pompano ( Trachinotus blochii ) were subjected to bidirectional FAO modulation for 90 days using mildronate (THP, FAO inhibition) or l -carnitine (L-CN, FAO enhancement). Growth performance, tissue composition, plasma metabolites, histology, and integrated liver-muscle metabolomics-transcriptomics were analyzed to assess tissue-specific metabolic remodeling. Both FAO inhibition and enhancement improved final body weight and specific growth rate. FAO inhibition promoted adiposity, reduced muscle protein and glycogen, increased lactic acid/LDH and oxidative damage, and induced liver depletion of carnitine/acylcarnitines with accumulation of TCA intermediates. In contrast, FAO enhancement reduced lipid deposition, enhanced lipid catabolism, and promoted protein retention and glycogen storage. Multi-omics analysis further showed that liver remodeling reflected carbon-flux reallocation between FAO, TCA activity and glycogen deposition, whereas muscle remodeling shifted between FAO inhibition-associated catabolic/stress responses to FAO enhancement-associated anabolic and proteostasis programs. Overall, our results demonstrate that FAO capacity, not only lipid supply, determines the shift toward protein accumulation or adiposity in golden pompano, and reveal a coordinated yet tissue-specific metabolic remodeling in liver and muscle that supports effective protein sparing while reducing reliance on costly marine protein resources.