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Title: DIETARY PROTEIN AND LACTOSE INCREASE TRANSLATION INITIATION FACTOR ACTIVATION AND TISSUE PROTEIN SYNTHESIS IN NEONATAL PIGS

Author
item FRANK, JASON - BAYLOR COLL OF MEDICINE
item ESCOBAR, JEFFERY - BAYLOR COLL OF MEDICINE
item Suryawan, Agus
item NGUYEN, HANH - BAYLOR COLL OF MEDICINE
item KIMBALL, SCOT - PENN STATE COLL OF MED
item JEFFERSON, LEONARD - PENN STATE COLL OF MED
item Davis, Teresa

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/6/2005
Publication Date: 2/1/2006
Citation: 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.

Interpretive Summary: It is believed that the consumption of a high protein diet by very low birth weight infants will increase body weight and muscle growth. Increasing body weight and muscle growth in these infants is very important for proper development and survival. In this study, we used a piglet model to study the effects of dietary protein and lactose on muscle growth. Piglets were fed milk diets containing three different levels of protein and two levels of lactose. The dietary proteins levels were below, adequate, or in excess of the requirement to maximize body weight gain. In these piglets, we measured body weight gain, muscle growth, and the activation level of signaling components in the cell that regulate muscle growth. Our results show that piglet body weight and muscle growth increase with dietary protein and lactose intake. The increase in muscle growth occurs because specific signaling components in the cells are stimulated. These results indicate body weight and muscle growth in piglets are influenced by dietary protein and lactose intake. While it is very important to provide protein and lactose in the diet, feeding protein above the nutritional requirement, does not further increase body weight or muscle growth in piglets. The results from this study in baby pigs will help us identify the mechanisms that regulate muscle growth in neonates. Understanding these mechanisms will lead to better feeding strategies that improve development and survival of very low birth weight infants.

Technical Abstract: Protein synthesis and eukaryotic initiation factor (eIF) activation are increased in muscle and liver of pigs parenterally infused with amino acids and insulin. To examine the effects of enteral protein and carbohydrate on protein synthesis, pigs (n = 42, 1.7 kg body wt) were fed isocaloric milk diets containing three levels of protein (5, 15, and 25 g.kg body wt(-1).day(-1)) and two levels of lactose (low = 11 and high = 23 g.kg body wt(-1).day(-1)) from 1 to 6 days of age. On "day 7", pigs were gavage fed after 4-h food deprivation, and tissue protein synthesis rates and biomarkers of mRNA translation were assessed. Piglet growth and protein synthesis rates in muscle and liver increased with dietary protein and plateaued at 15 g.kg body wt(-1).day(-1) (P < 0.001). Growth tended to be greater in high-lactose-fed pigs (P = 0.07). Plasma insulin was lowest in pigs fed 5 g.kg body wt(-1).day(-1) protein (P < 0.0001). Plasma branched-chain amino acids increased as protein intake increased (P < 0.0001). Muscle (P < 0.001) and liver (P < or = 0.001) ribosomal protein S6 kinase-1 and eIF4E-binding protein phosphorylation increased with protein intake and plateaued at 15 g.kg body wt(-1).day(-1). The results indicate that growth and protein synthesis rates in neonatal pigs are influenced by dietary protein and lactose intake and might be mediated by plasma amino acids and insulin levels. However, feeding protein well above the piglet's requirement does not further stimulate the activation of translation initiation or protein synthesis in skeletal muscle and liver.