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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #141844
Title: FEEDING STIMULATES PROTEIN SYNTHESIS IN MUSCLE AND LIVER OF NEONATAL PIGS THROUGH AN MTOR-DEPENDENT PROCESS

Author
item KIMBALL, SCOT - PENN STATE UNIV
item JEFFERSON, LEONARD - PENN STATE UNIV
item NGUYEN, HANH - BAYLOR COLL OF MED
item SURYAWAN, AGUS - BAYLOR COLL OF MED
item BUSH, JILL - BAYLOR COLL OF MED
item Davis, Teresa

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/6/2000
Publication Date: 11/1/2000
Citation: Kimball, S.R., Jefferson, L.S., Nguyen, H.V., Suryawan, A., Bush, J.A., Davis, T.A. 2000. Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent process. American Journal of Physiology - Endocrinology and Metabolism. 279(5):E1080-E1087

Interpretive Summary: The muscles of healthy newborns grow at a very rapid rate. We have previously shown that the rapid growth of muscles in newborns is due to their muscles responding to feeding by rapidly and profoundly increasing the synthesis of muscle proteins. We have shown that it is the rise in amino acids and the hormone, insulin, which occurs after eating that stimulates the synthesis of proteins in muscle. In this study in which we used newborn pigs as a model of the human, we used a chemical which blocks a cellular signaling pathway that insulin and amino acids have been shown previously to use to stimulate protein synthesis in cells cultured in a test tube. We found that this chemical blocked the stimulation of protein synthesis in muscle of newborn pigs. These results prove that muscles of healthy newborns use this cellular signaling pathway to grow when they eat a meal. 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: Protein synthesis is repressed in both skeletal muscle and liver after a short-term fast and is rapidly stimulated in response to feeding. Previous studies in rats and pigs have shown that the feeding-induced stimulation of protein synthesis is associated with activation of the 70-kDa ribosomal protein S6 kinase (S6K1) as well as enhanced binding of eukaryotic initiation factor eIF4E to eIF4G to form the active eIF4F complex. In cells in culture, hormones and nutrients regulate both of these events through a protein kinase termed the mammalian target of rapamycin (mTOR). In the present study, the involvement of mTOR in the feeding-induced stimulation of protein synthesis in skeletal muscle and liver was examined. Pigs at 7 days of age were fasted for 18 h, and then one-half of the animals were fed. In addition, one-half of the animals in each group were administered rapamycin (0.75 mg/kg) 2 h before feeding. The results reveal that treating 18-h fasted pigs with rapamycin, a specific inhibitor of mTOR, before feeding prevented the activation of S6K1 and the changes in eIF4F complex formation observed in skeletal muscle and liver after feeding. Rapamycin also ablated the feeding-induced stimulation of protein synthesis in liver. In contrast, in skeletal muscle, rapamycin attenuated, but did not prevent, the stimulation of protein synthesis in response to feeding. The results suggest that feeding stimulates hepatic protein synthesis through an mTOR-dependent process involving enhanced eIF4F complex formation and activation of S6K1. However, in skeletal muscle, these two processes may account for only part of the stimulation of protein synthesis, and thus additional steps may be involved in the response.