Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/28/2005
Publication Date: 6/1/2005
Citation: Frank, J.W., Escobar, J., Suryawan, A., Kimball, S.R., Nguyen, H.V., Jefferson, L.S., Davis, T.A. 2005. Protein synthesis and translation initiation factor activation in neonatal pigs fed increasing levels of dietary protein. Journal of Nutrition. 135(6):1374-1381. Interpretive Summary: Low birth weight infants grow better when fed high levels of protein in the diet than they do if fed low levels of protein in the diet. To better understand the mechanism by which dietary protein increases growth, we used baby pigs, which are the best model of human infants, and fed them marginal, adequate, or excess levels of protein in the diet for 5 days. We measured the rate at which proteins are synthesized in different tissues of the body and the activation level of components in the cell that regulate protein synthesis. We found that protein synthesis rates in all tissues are increased when diets that contain either marginal, adequate, or excess levels of protein are fed to infant pigs. The increase in protein synthesis occurs because specific signaling components in the cells are stimulated. However, feeding a very high protein diet that is greater than the known protein requirement does not further increase protein synthesis or further stimulate the signaling components in cells. These findings in baby pigs are important because by identifying the mechanism that regulates muscle growth in neonate we can learn valuable information so that we can develop better strategies for the nutritional management of very low birth weight infants.
Technical Abstract: Limited data suggest that the growth of low-birth-weight infants is enhanced by feeding a high-protein diet; however, the mechanisms involved in the effect have not been delineated. To identify these mechanisms, 34 pigs were fed from 2 to 7 d of age [60 g dry matter/(kg body weight . d)] isocaloric milk diets that contained levels of dietary protein that were marginal, adequate, and in excess of the piglets protein requirement (21, 33, and 45% of dry matter, respectively). Dietary protein replaced lactose and fat on an isocaloric basis. Fractional protein synthesis rates, various biomarkers of translational regulation, and plasma glucose and insulin levels were measured in overnight food-deprived and fed pigs. Mean daily weight gain of pigs fed the 33 and 45% protein diets was greater than that of pigs fed the 21% protein diet (P < 0.01). Plasma glucose (P = 0.07) and insulin (P < 0.01) levels decreased as dietary protein increased 60 min after feeding. Protein synthesis rates in longissimus dorsi, gastrocnemius, masseter, heart, liver, kidney, jejunum, and pancreas were greater in the fed than in the food-deprived state (P < 0.01). Protein synthesis in skeletal muscle did not change with protein intake in the fed state, but decreased quadratically (P < 0.01) with increasing dietary protein in the food-deprived state. Protein kinase B, ribosomal protein S6 kinase 1(S6K1), and eukaryotic initiation factor (eIF) 4E binding protein-1 (4E-BP1) were more phosphorylated, and assembly of the inactive eukaryotic initiation factor 4E . 4E-BP1 complex in muscle and liver was reduced in the fed state (P < 0.001) and were not consistently affected by dietary protein level. The results suggest that feeding stimulates protein synthesis, and this is modulated by the activation of initiation factors that regulate mRNA binding to the ribosomal complex. However, the provision of a high-protein diet that exceeds the protein requirement does not further enhance protein synthesis or translation initiation factor activation.