Verification of the lactogenic effect of egg white peptides: regulation of key proteins involved in milk synthesis

BACKGROUND: Insufficient lactation represents a critical global public health concern, profoundly impacting infant growth and development. Food-derived egg white peptides (EWPs) are believed to have lactation-promoting effects; however, the molecular mechanisms underlying these effects remain unclear. RESULTS: This research investigates EWPs as a potential functional food component to enhance lactation and dissects the underlying mechanisms using a combined phenotypic and omics approach in an overload breastfeeding mouse model. Our phenotypic analyses reveal that dietary supplementation with EWPs significantly increases milk production and promotes mammary gland epithelial cell proliferation. Additionally, it effectively mitigates maternal reproductive and lactational burdens, thereby supporting post-partum physiological recovery. Transcriptomic and western blot analyses further demonstrate that EWPs are associated with lactogenic effects through modulation of both direct and indirect signaling pathways. Direct pathways include the prolactin, oxytocin, and insulin signaling cascades, which regulate milk synthesis and secretion. Indirect pathways involve AMPK, JAK-STAT, glycolysis, and gluconeogenesis, which modulate energy metabolism and cellular homeostasis to support lactation. At the protein level, EWPs upregulate the expression of STAT5A, PFKM, and CRYAB, which are key regulators of milk protein synthesis. CONCLUSION: Collectively, our findings establish EWPs as a novel functional food supplement that may improve lactation performance and support maternal-infant health. This work provides a mechanistic framework for the development of personalized nutritional interventions to address lactation insufficiency, offering a promising strategy to improve outcomes for mothers and infants.