The mechanisms by which amino acids are transferred across the human placenta are fundamental to our understanding of foetal nutrition. Amino acid transfer across the human placenta is dependent on transport across both the microvillous and basal plasma membranes of the placental syncytiotrophoblast, and on metabolism within the syncytiotrophoblast. Although the principles underlying uptake of amino acids across the microvillous plasma membrane are well understood, the extent to which amino acids are metabolised within human placenta and the mechanisms by which amino acids are transported out of the placenta across the basal plasma membrane are not well understood. Understanding the mechanisms and regulation of amino acid transport is necessary to understand the causes of intrauterine growth restriction in human pregnancy.

Poor early growth is associated with Type II diabetes, hypertension and other features of the metabolic syndrome in adulthood. It has been suggested that this results from the development of a thrifty phenotype by a malnourished fetus. Such a phenotype would predispose the offspring to the development of obesity if born into conditions of over-nutrition. The present study aimed to determine if early nutrition affected subsequent development of obesity. Mice were established as follows: (a) controls (offspring of control dams), (b) recuperated (offspring of dams fed a low-protein diet during pregnancy, but nursed by control dams) and (c) postnatal low-protein (offspring of control dams nursed by low-protein-fed dams). Mice were weaned on to standard laboratory chow or a cafeteria diet. Recuperated offspring, although smaller at birth ( P <0.01), caught up and exceeded the weight of control offspring by 7 days of age ( P <0.001). Postnatal low-protein offspring were smaller than controls by 7 days of age ( P <0.001). Recuperated animals gained more weight than controls when given free access to a highly palatable diet ( P <0.01). Postnatal low-protein animals showed no additional weight gain when given a highly palatable diet compared with chow-fed litter-mates. These results suggest that the early environment has long-term consequences for weight gain. These programmed responses are powerful enough to block excess weight gain from a highly palatable diet and, thus, have major implications for the drug-free regulation of food intake and obesity.

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