Location: Children's Nutrition Research CenterTitle: The abundance and activiation of mTORC1 regulators in skeletal muscle of neonatal pigs are modulated by insulin, amino acids, and age) Author
Submitted to: Journal of Applied Physiology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 8/11/2010
Publication Date: 8/19/2010
Citation: Suryawan, A., Davis, T.A. 2010. The abundance and activiation of mTORC1 regulators in skeletal muscle of neonatal pigs are modulated by insulin, amino acids, and age. Journal of Applied Physiology. 109(5):1448-1454. Interpretive Summary: Signaling components are crucial for the regulation of protein synthesis. From previous studies we found that the activation of these components is higher in neonatal pigs when compared to older pigs which parallel the higher protein synthesis rates in neonatal pigs. In this study, we examined the effect of insulin, amino acids, and age on the abundance and the activation of these signaling components. The components that we examined were the regulators of mammalian target of rapamycin complex 1 (mTORC1) signaling. Although the abundance of these components was similar in all treatments, the activation of PRAS40 (an inhibitor) is lower and the activation of PLD1 and Rag GTPases (activators) was higher in younger pigs compared to older pigs. This is consistent with higher activation of mTORC1 and protein synthesis in neonatal pigs. In conclusion, this study shows that during the neonatal period, the higher ability to grow is partly due to the higher activation of components of protein synthesis.
Technical Abstract: Mammalian target of rapamycin complex 1 (mTORC1) signaling is crucial for the regulation of protein synthesis. Most of known mTORC1 regulators have been isolated and characterized using cell culture systems, and the physiological roles of these regulators have not been fully tested in vivo. Previously we demonstrated that the insulin (INS) and amino acid (AA)-induced activation of mTORC1 is developmentally regulated in skeletal muscle (Suryawan A et al. "Am J Physiol Endocrinol Metab" 293: E1597–E1605, 2007). The present study aimed to characterize in more detail the effects of the postprandial rise in INS and AA on the activation and abundance of mTORC1 regulators in muscle and how this is modified by development. Overnight fasted 6- and 26-day-old pigs were studied during "1") euinsulinemic-euglycemic-euaminoacidemic conditions (control), "2") euinsulinemic-euglycemic-hyperaminoacidemic clamps (AA), and "3") hyperinsulinemic-euglycemic-euaminoacidemic clamps (INS). INS, but not AA, enhanced the PRAS40 phosphorylation, and this effect was greater in 6- than in 26-day old pigs. Phospholipase D1 (PLD1) abundance and phosphorylation, and the association of PLD1 with Ras homolog enriched in brain (Rheb), were greater in the younger pigs. Neither INS, AA, nor age altered the abundance of Rheb, vacuolar protein sorting 34 (Vps34), or FK506-binding protein 38 (FKBP38). Although INS and AA had no effect, the abundance of ras-related GTP binding B (RagB) and the association of RagB with Raptor were greater in 6- than in 26-day-old pigs. Neither INS, AA, nor age altered AMPK-induced phosphorylation of Raptor. Our results suggest that the enhanced activation of mTORC1 in muscle of neonatal pigs is in part due to regulation by PRAS40, PLD1, and the Rag GTPases.