Metabolic regulation of infant growth

Growth characteristics during periods of early developmental plasticity are closely linked with later health outcomes including physical and cognitive performance, and with disease risks. Evidence is particularly convincing for early growth modulation of later risks of obesity, adiposity and associated non-communicable diseases, e.g. type 2 diabetes, hypertension, cardiovascular diseases, and asthma. Infant growth is modulated by genetic, epigenetic, inflammatory, endocrine, nutritional and metabolic factors. Improved nutrition offers major preventive opportunities.

High protein intakes in infancy can induce excessive early weight gain (1, 2) and increased later obesity (3). Targeted metabolomic profiling of small molecules <1.5 KDa in biological samples, which represent substrates, intermediates and products of biological processes, offer insights into underlying mechanisms. Using high performance liquid chromatography coupled to triple quadrupole mass spectrometry (LC-MS/MS) we precisely quantify several hundreds of molecules in small volumes of 10-50 µl plasma. These analyses show that high protein supplies with conventional infant formulae markedly increase infant plasma concentrations of indispensable amino acids, particularly of branched-chain amino acids (BCAA) which can upregulate the mTOR-pathway and thereby induce protein and lipid synthesis, and excessive growth (4).

With conventional protein intakes, the infant’s capacity of BCAA breakdown via BC-α-ketoacid dehydrogenase is exceeded, while the initiation of fatty acid beta-oxidation is suppressed, which may enhance body fat deposition (4). High protein supplies also induce increased tyrosine concentrations, which predict insulin resistance in obese children (5). High protein supplies enhance the secretion of both growth factors insulin and IGF-1 (6). A path model analysis shows a stronger response of insulin to amino acids, and very different effects of individual amino acids (7). Moreover, the energetic efficiency of infant formula for weight and length gain depends particularly on the protein quality provided (8). Together, these results lead us to conclude that improving both the quantity and quality of protein intakes may be of considerable importance for achieving optimal infant growth.