Adipocyte glutamine production and lactation

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Glutamine (together with glutamate) make up 20% of the amino acids in protein and are 50% of the non-protein amino acids in milk. As lactation progresses the concentration of most free amino acids in milk stay relatively constant but the concentrations of free glutamate and glutamine increase by 40% and 350% respectively. These free amino acids are thought to function by an immunomodulating mechanism to protect against neonatal allergies and infections. Supplementation of glutamine to lactating pigs increases the free glutamine in milk and supplementation to suckling piglets improves immune and intestinal function. Thus, the levels of free glutamine and glutamate in milk may not be optimal and free glutamine may play important roles in neonatal immune function and intestinal health. The lactating mammary gland takes up large amounts of glutamine from the circulation but up to 50% of the glutamine in milk is synthesized with the gland through the action of glutamine synthetase. Preliminary data suggest that adipocytes within the mammary gland are the source of this glutamine production. We developed a mouse strain where glutamine synthetase was ablated in adipocytes (AT Glul-/-). Arterio-venous difference measurements and stable isotope tracing will be used in these mice to determine the contribution of glutamine production by adipocytes to glutamine metabolism during lactation. Similar studies will be carried out to determine how adipocyte glutamine synthesis responds to dietary and environmental changes. Glutamine synthetase in adipose tissue is decreased during obesity which may impair mammary epithelial proliferation. Using the AT Glul-/- mice the role of glutamine production in adipose tissue will be determined in diet-induced obese mice. The work will be the first application of the ablation of a key metabolic gene to the study of amino acid metabolism in lactation. The long-term goals are to understand the function of large amounts of glutamine and glutamate in milk which may lead to changes both in maternal diet and the composition of infant formula.