Dose-dependent arginine availability is associated with metabolic remodeling and immune phenotypes during development.

BACKGROUND: L-Arginine is a semi-essential, functional amino acid crucial for fetal growth, metabolic regulation, and early-life immune ontogeny. However, how variations in maternal arginine availability influence neonatal metabolic remodeling and long-term immune development remains incompletely understood. METHODS: Female Sprague-Dawley rats were fed amino acid-defined diets with graded arginine levels during gestation and lactation. Neonatal hepatic metabolism was profiled by 1H NMR-based metabolomics, and splenic immune responses and immune cell populations were evaluated in neonatal and adult offspring. RESULTS: Arginine availability was associated with differences in neonatal hepatic metabolite profiles. A physiological level (6 g/kg diet) was associated with a balanced metabolic state, whereas deficiency (0 g/kg) and higher intake (24 g/kg) were associated with altered metabolic profiles. Deficiency was associated with features consistent with a catabolic state, including increased ketone bodies. Higher intake was associated with altered amino acid metabolism, including elevations in branched-chain amino acids and lactate. These metabolic patterns were accompanied by coordinated alterations in immune parameters that persisted into adulthood. CONCLUSION: Arginine availability was associated with non-linear, dose-dependent metabolic alterations and coordinated immune phenotypes during development, providing insight into the association between early-life metabolic remodeling and long-term immune programming.