2007 Annual Report
Understanding the Role of Retinoic Acid: Greater insight is needed on our understanding of human blood and vascular development, and the role of specific nutrients such as Vitamin A in the regulation of these processes. Children's Nutrition Research Center researchers determined that retinoic acid is needed to specify a subset of endothelial cells to become blood-forming, or hemogenic, endothelium. These findings were learned from cellular and molecular studies in the mouse embryonic model system. This is important since we now know more about the role of Vitamin A during the development of blood vessels and blood. [NP 107, Component 2 Bioavailability of Nutrients and Food Components] (CNRC Project 3)
Glucose Stimulates Protein Synthesis in Skeletal Muscle through an AMPK and mTOR Independent Process: Children's Nutrition Research Center researchers have demonstrated that skeletal muscle protein synthesis is increased in newborns, partially due to an increased response to insulin and amino acids upon eating. Our lab examined the role of glucose in the rise in skeletal muscle protein synthesis that occurs after eating meals (postprandial). The results showed that the postprandial rise in glucose, independent of insulin and amino acids, stimulates protein synthesis in newborns and this response occurs by AMPK (activated protein kinase) and mTOR (mammalian target of rapamycin) independent pathways. These results demonstrate that multiple nutrient factors impact protein synthesis, and thus, growth in young animals. This research emphasizes the importance of a balanced carbohydrate and protein containing diet in the growth of skeletal muscle in the newborn child, and provides valuable information to enhance strategies for the nutritional management of low birth weight infants. [NP 107, Component 2 Bioavailability of Nutrients and Food Components] (CNRC Project 2)
Inadequate Satellite Cell Replication Compromises Muscle Regrowth Following Postnatal Nutrient Restriction: When muscle growth is reduced by nutritional deficiencies during the suckling period, resuming feeding of that animal accelerates the rate of muscle growth but not sufficiently to restore the animal's muscle mass. This impediment to muscle growth is likely due to a limited increase in myonuclear number as a result of the limited capacity of the existing satellite cells to multiply. At the Children's Nutrition Research Center researcher’s in Houston, TX, mouse dams were fed a low-protein diet during lactation, resulting in pups with muscles weighing 80% of the control's muscle weight. When the low-protein diet fed mice were fed a normal diet, muscle mass gain accelerated to age appropriate levels, however remained proportionately smaller than the control's muscles. This research is important since it addresses the potential mechanism that in mammals, birth weight and early newborn growth rates are significant determinants of adult muscle mass. [NP107, Component 2 Bioavailability of Nutrients and Food Components] (CNRC Project 4)
Researchers Identify Leads to Fatty Liver: Children's Nutrition Research Center researchers showed that chronic (parenteral) intravenous nutrition leads to hepatic steatosis or fatty liver, thus this finding suggests that fatty liver may contribute to liver dysfunction and metabolic problems associated with intravenous feedings in premature infants. Utilizing the newborn piglet as a model, animals were fed exclusively intravenously through a vascular catheter for 7 days and compared to those fed orally with a milk-based formula. Our lab discovered that intravenous nutrition resulted in a higher content of fat in liver tissue and that this was associated with increased death of liver cells. These studies show that a relatively short period of intravenous nutrition can lead to fatty liver and perhaps dysfunction, and further studies will be pursued to specifically assess how fatty liver might contribute to poor liver function in this population of infants. We hope to use these research findings to design nutritional approaches to reduce fatty liver and maintain healthy liver function. [NP107, Component 4 Nutrient Requirements] (CNRC Project 1)
Generating GLP-2 Receptor Conditional Knockout Mouse Model: Children's Nutrition Research Center researchers have completed the full construct for generating glucagon-like peptide 2 (GLP-2) receptor conditional knockout mice. This construct was generated through utilization of the Bacterial Artificial Chromosomes (BAC) recombineering approach and electroporated into the mouse embryonic cells. After screening, the embryonic stem cells were microinjected into blastocytes to obtain the glp2r conditional knockout mice. These knockout mice will be used by researchers to establish physiological significance and signaling network of GLP-2 receptor in controlling gut development, growth, and function. [NP107, Component 4 Nutrient Requirements] (CNRC Project 6)
Establishment of Primary Neuron Culture Model: Children's Nutrition Research Center researchers have developed a primary culture of central and peripheral neurons that play a significant role in the control of intestinal function. Our lab has found that the GLP-2R protein was localized to the spinal ganglion neurons and hippocampal (brain) neurons, and the primary cultured neurons respond to the exogenous GLP-2. Development of this primary culture model is important since it can be used to address at cellular and molecular levels how the GLP-2 receptor functions, thus furthering science. [NP107, Component 4 Nutrient Requirements] (CNRC Project 6)
Wang, H., Khaoustov, V.I., Krishnan, B., Cai, W., Stoll, B., Burrin, D.G., Yoffe, B. 2006. Total parenteral nutrition induces liver steatosis and apoptosis in neonatal piglets. Journal of Nutrition. 136:2547-2552.
Lambert, B.D., Filip, R., Stoll, B., Junghans, P., Derno, M., Hennig, U., Souffrant, W.B., Pierzynowski, S., Burrin, D.G. 2006. First-pass metabolism limits the intestinal absorption of enteral alpha-ketoglutarate in young pigs. Journal of Nutrition. 136:2779-2784.
Burrin, D.G., Stoll, B. 2007. Emerging aspects of gut sulfur amino acid metabolism. Current Opinion in Clinical Nutrition and Metabolic Care. 10:63-68.
Burrin, D.G., Stoll, B., Guan, X., Cui, L., Chang, X., Hadsell, D. 2007. GLP-2 rapidly activates divergent intracellular signaling pathways involved in intestinal cell survival and proliferation in neonatal piglets. American Journal of Physiology - Endocrinology and Metabolism. 292:E281-E291
Suryawan, A., Escobar, J., Frank, J.W., Nguyen, H.V., Davis, T.A. 2006. Developmental regulation of the activation of signaling components leading to translation initiation in skeletal muscle of neonatal pigs. American Journal of Physiology, Endocrinology and Metabolism. 291(4):E849-E859.
Gingras, A-A., White, P.J., Chouinard, P.Y., Julien, P., Davis, T.A., Dombrowski, L., Couture, Y., Dubreuil, P., Myre, A., Bergeron, K., Marette, A., Thivierge, M.C. 2007. Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt-mTOR-S6K1 pathway and insulin sensitivity. Journal of Physiology. 579(Pt 1):269-284.
Frank, J.W., Escobar, J., Nguyen, H.V., Jobgen, S.C., Jobgen, W.S., Davis, T.A., Wu, G. 2007. Oral "N"-Carbamylglutamate supplementation increases protein synthesis in skeletal muscle of piglets. Journal of Nutrition. 137(2):315-319.
Jeyapalan, A.S., Orellana, R.A., Suryawan, A., O'Connor, P.M.J., Nguyen, H.V., Escobar, J., Frank, J.W., Davis, T.A. 2007. Glucose stimulates protein synthesis in skeletal muscle of neonatal pigs through an AMPK- and mTOR-independent process. American Journal of Physiology Endocrinology and Metabolism. 293(2):E595-E603.
Orellana, R.A., Kimball, S.R., Suryawan, A., Escobar, J., Nguyen, H.V., Jefferson, L.S., Davis, T.A. 2007. Insulin stimulates muscle protein synthesis in neonates during endotoxemia despite repression of translation initiation. American Journal of Physiology Endocrinology and Metabolism. 292(2):E629-E636.
Orellana, R.A., O'Connor, P.M.J., Bush, J.A., Suryawan, A., Thivierge, M.C. Nguyen, H.V., Fiorotto, M.L., Davis, T.A. 2006. Modulation of muscle protein synthesis by insulin is maintained during neonatal endotoxemia. American Journal Physiology - Endocrinology and Metabolism. 291(1):E159-E166.
Suryawan, A., Frank, J.W., Nguyen, H.V., Davis, T.A. 2006. Expression of the TGF-Beta family of ligands is developmentally regulated in skeletal muscle of neonatal rats. Pediatric Research. 59(2):175-179.
Frank, J.W., Escobar, J., Suryawan, A., Nguyen, H.V., Kimball, S.R., Jefferson, L.S., Davis, T.A. 2006. Dietary protein and lactose increase translation initiation factor activation and tissue protein synthesis in neonatal pigs. American Journal Physiology - Endocrinology and Metabolism. 290(2):E225-E233.
Thymann, T., Burrin, D.G., Tappenden, K.A., Bjornvad, C.R., Jensen, S.K., Sangild, P.T. 2006. Formula-feeding reduces lactose digestive capacity in neonatal pigs. British Journal of Nutrition. 95:1075-1081.
Suryawan, A., Davis, T.A. 2005. Developmental regulation of protein kinase B activation is isoform specific in skeletal muscle of neonatal pigs. Pediatric Research. 58(4):719-724.
Shulman, R.J., Eakin, M.N., Jarrett, M., Czyzewski, D.I., Zelter, L.K. 2007. Characteristics of pain and stooling in children with recurrent abdominal pain. Journal of Pediatric Gastroenterology and Nutrition. 44(2):203-208.
Thakkar, K., Gilger, M.A., Shulman, R.J., El Serag, H.B. 2007. EGD in children with abdominal pain: A systematic review. American Journal of Gastroenterology. 102:654-661.
Carter, B.A., Shulman, R.J. 2007. Mechanisms of disease: Update on the molecular etiology and fundamentals of parenteral nutrition associated cholestasis. Nature Clinical Practice Gastroenterology & Hepatology. 4(5):277-287.
Riedijk, M.A., Stoll, B., Chacko, S., Schierbeek, H., Sunehag, A.L., Van Goudoever, J.B., Burrin, D.G. 2007. Methionine transmethylation and transsulfuration in the piglet gastrointestinal tract. Proceedings of the National Academy of Sciences. 104(9):3408-3413.
Ramirez, A., Wong, W.W., Shulman, R.J. 2006. Factors regulating gastric emptying in preterm infants. Journal of Pediatrics. 149(4):475-479.
Czyzewski, D.I., Eakin, M.N., Lane, M.M., Jarrett, M., Shulman, R.J. 2007. Recurrent abdominal pain in primary and tertiary care: differences and similarities. Children's Health Care. 36(2):137-153.
Burr, R.L., Motzer, S.A., Chen, W., Cowan, M.J., Shulman, R.J., Heitkemper, M.M. 2006. Heart rate variability and 24-hour minimum heart rate. Biological Research for Nursing. 7(4):256-267.