Monney, B.; Ewaoluwagbemiga, E. O.; Kasper, C.

Dietary protein restriction challenges the allocation of amino acids to growth and other physiological functions and therefore requires coordinated metabolic adaptation. Domestic pigs provide an informative system in which to study such responses, because nitrogen retention directly affects lean growth and can be quantified accurately under controlled feeding and housing conditions. Under reduced-protein diets, pigs differ in how effectively they retain nitrogen, and this variation has a genetic basis, making them well suited to investigate the molecular regulation of nitrogen use efficiency (NUE). Here, we characterise differential gene expression and enriched pathways in liver and skeletal muscle of more than 80 pigs with two divergent NUE phenotypes (high and low) maintained under the same protein-reduced, ad libitum dietary conditions. The two NUE phenotypes were clearly distinct at the transcriptomic level, with 177 differentially expressed genes in the liver and 133 in the muscle. In the liver, differential expression and enrichment analyses indicate reduced amino acid catabolism, lower inflammatory and detoxification activity, and a metabolic state that favours lipid processing and insulin-related regulation over the use of amino acids as energy sources. In skeletal muscle, they point to reduced lipid uptake, lower reliance on amino acid oxidation, and a greater emphasis on protein synthesis, translational regulation, mitochondrial energy metabolism, and growth-related processes. These gene-level patterns were supported and extended by pathway and gene-set enrichment analyses. Together, the results suggest that high and low-NUE pigs differ through coordinated, tissue-specific molecular adaptations. Overall, variation in NUE appears to reflect coordinated, tissue-specific differences in how nutrients are allocated between energy use, storage, and lean tissue growth.