Dietary protein intake affects amino acid and acylcarnitine metabolism in infants aged 6 months

Context: The protective effect of breastfeeding against later obesity may be explained by the lower protein content compared to formula milk. However, the metabolic mechanisms remain unknown. Objective: We studied the metabolic response to a higher or lower protein supply in infancy. Design and Setting: The Childhood Obesity Project (CHOP) study is a double-blind, randomized, multicenter intervention trial. Infants were randomized to receive a higher (HP) or lower protein (LP) content infant formula or were breastfed. Patients and Interventions: Plasma samples of 691 infants who received formula milk with different protein content (HP, 2.05 g/100ml; LP, 1.25 g/100ml) or were breastfed were collected. Main Outcome Measures: Changes in plasma amino acid and acylcarnitine concentrations of 6-months old infants according to different dietary protein supply were determined by LC-MS/MS. Results: Twenty-nine metabolites differed significantly between the formula groups. Branched-chain amino acids (BCAA) were the most discriminant metabolites. Their degradation products, the short-chain acylcarnitines C3, C4 and C5, were also significantly elevated in the HP group. A breakpoint analysis confirmed that with increasing BCAA, the ratio between acylcarnitines and BCAA decreases. Long-chain acylcarnitines were decreased in HP-infants. Conclusions: BCAA seem to play a pivotal role in the effect of a high protein diet on ß-oxidation and fat storage. We provide new evidence for a possible saturation of the BCAA degradation pathway that may represent the mechanism by which high protein intake affects the metabolic regulation. Moreover, it appears to inhibit the initial step of the ß-oxidation, thus leading to high early weight gain and body fat deposition.