Title: Methods of measuring nutrient substrate utilization using stable isotopes Authors
Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: April 15, 2006
Publication Date: June 3, 2006
Citation: Sunehag, A.L., Haymond, M.W. 2006. Methods of measuring nutrient substrate utilization using stable isotopes. In: Thureen, P., Hay W., Jr., editors. Neonatal Nutrition and Metabolism. 2nd Edition. Cambridge: Cambridge University Press. p. 617-630. Technical Abstract: Following cessation of the transplacental flow of nutrients, most healthy term newborn infants promptly initiate hepatic glucose production to meet their high glucose demands and maintain normoglycemia. Since the hepatic glycogen content is limited, the neonate becomes dependent on gluconeogenesis as the primary mechanism to maintain euglycemia within a few hours of fasting. The rapid postnatal increase in plasma concentrations of glycerol and free fatty acids, high glycerol turnover rates, and decreasing respiratory quotient indicate that lipolysis and lipid oxidation increase immediately following birth, thus demonstrating the importance of lipid as oxidative substrates. Lipids also contribute to the maintenance of glucose homeostasis in infants in that hydrolysis of triglycerides generates glycerol, which is used directly for glucose production via gluconeogenesis, and free fatty acids (FFA), which upon hepatic '-oxidation provide energy to drive the gluconeogenic process. Endogenous as well as exogenous amino acids are of great importance in the rapidly growing neonate since they serve as the building blocks for the body proteins. Further, after deamination a number of amino acids are also utilized as oxidative fuel and gluconeogenic substrate. Metabolic research in newborn infants is limited by several constraints. The studies must be minimally invasive, the blood samples very small, and each study must provide maximal information possible, because of the difficulty in recruiting newborns for studies. The use of compounds labeled with stable isotopes analyzed by gas chromatography-mass spectrometry (GCMS) or isotope ratio-mass spectrometry (IRMS) fulfill these requirements, thus providing a very valuable tool for dynamic studies of neonatal metabolism. In this chapter, we describe how these techniques can be used to explore carbohydrate, lipid, and protein metabolism in newborn infants.