Breastfeeding induces a different metabolic and endocrine response than feeding conventionalinfant formula, and it has also been associated with slower weight gain and reduceddisease risk in later life. The underlying programming mechanisms remain to beexplored. Breastfeeding has been reported to induce lower levels of insulin, insulin-likegrowth factor-1 and some amino acids (AAs) than formula feeding. In the Childhood ObesityProject (CHOP), infants fed a conventional protein-rich formula had a higher BMIat 2 and 6 years than those fed a protein-reduced formula. At 6 months, higher proteinintakes induced increased plasma concentrations of branched-chain AAs (BCAAs) andtheir oxidation products, short-chain acylcarnitines. With increasing BCAA levels, theseshort-chain acylcarnitines increased proportionally only until a break point was reached,after which BCAAs seemed to escape their degradation. The resulting marked elevationin BCAA levels with high-protein (HP) intakes appears to contribute to increased insulinlevels and to affect β-oxidation of fatty acids. The ratios of long-chain acylcarnitines to freecarnitine decreased in infants who received a HP formula, which indicates a reduced initiationof β-oxidation. We conclude that HP intakes inducing high BCAA plasma levels mayinhibit fat oxidation and thereby enhance body fat deposition and adiposity.