Multiple essential amino acids regulate mammary metabolism and milk protein synthesis in lactating dairy cows

Improving of nitrogen (N) utilization efficiency in dairy production systems could help reduce feed costs and alleviate environmental concerns. A low protein content diet plus essential amino acids (EAA) supplementation is a widely used strategy to improve N efficiency in research and practice. Compared with multiple EAA supplementation, single EAA supplementation has been extensively studied and reviewed. However, the single EAA supplementation strategy does not consider flexible responses and interaction, imbalance, competition, or antagonism among EAA, which drove the original vision to supplement multiple EAA to dairy cows. In this review, we summarized literature supporting the theory that complete EAA mixtures have distinct advantages in improving milk protein yield (MPY). Except for branched-chain amino acids (BCAA), incomplete EAA mixtures increased MPY in diets that were relatively low in crude protein (CP) content or deficient in metabolizable protein (MP). Increased MPY is assisted by the integration of enhanced mammary blood/plasma flow, greater net uptake of AA, and activation of signaling pathways. These changes and multiple EAA profiles demonstrated plasticity in mammary protein metabolism and conformed to the demand-driven system controlling milk protein synthesis (MPS). In addition to signaling pathways such as the mechanistic target of rapamycin complex 1 pathway and integrated stress response, the unfolded protein response might also play an essential role in governing MPS at the molecular level. Considering the interactions between EAA and energy substrates, insulinemic and/or glucogenic substrates may potentiate the effect of multiple EAA on MPY. Incorporating a compelling amount of evidence, low CP content or MP deficient diets supplemented with multiple EAA should be more advantageous than supplementation with single EAA for improving N efficiency and further reducing feed costs, and relieving environmental concerns in the dairy industry. •Mammary gland can regulate its blood flow, uptake, and clearance according to demand.•Mammary gland has a demand-driven metabolism in controlling milk protein synthesis.•Multiple essential amino acids activated protein synthesis-related signaling pathways.•Multiple essential amino acids increased protein synthesis through mammary metabolism.•Multiple essential amino acids improved nitrogen efficiency in low crude protein diets.