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Title: Abundance of amino acid transporters involved in mTORC1 activation in skeletal muscle of neonatal pigs is developmentally regulated

Author
item SURYAWAN, AGUS - Children'S Nutrition Research Center (CNRC)
item NGUYEN, HANH - Children'S Nutrition Research Center (CNRC)
item ALMONACI, ROSEMARIE - Children'S Nutrition Research Center (CNRC)
item DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

Submitted to: Amino Acids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/15/2012
Publication Date: 5/30/2012
Citation: Suryawan, A., Nguyen, H.V., Almonaci, R.D., Davis, T.A. 2012. Abundance of amino acid transporters involved in mTORC1 activation in skeletal muscle of neonatal pigs is developmentally regulated. Amino Acids. 45:523-530.

Interpretive Summary: Amino acid (AA) transporters are carriers in the cell surface that serve to facilitate the AAs entering the cells. This process is crucial to ensure that after a meal, cells have enough AAs as substrates for protein synthesis to support growth. In this study, using baby pigs, we determine the effect of age, insulin, and AA infusion on the portion of AA transporters called SNAT2, SNAT3, LAT1, PAT1 and PAT2, an indication of their activity. Our results indicate that the portion of these transporters is higher in the younger pigs consistent their higher growth rate. Our study suggests that AA transporters can be used as valuable targets to improve growth during the newborn period.

Technical Abstract: Previously we demonstrated that the insulinand amino acid-induced activation of the mammalian target of rapamycin complex 1 (mTORC1) is developmentally regulated in neonatal pigs. Recent studies have indicated that members of the System A transporter (SNAT2), the System N transporter (SNAT3), the System L transporters (LAT1 and LAT2), and the proton-assisted amino acid transporters (PAT1 and PAT2) have crucial roles in the activation of mTORC1 and that the abundance of amino acid transporters is positively correlated with their activation. This study aimed to determine the effect of the postprandial rise in insulin and amino acids on the abundance or activation of SNAT2, SNAT3, LAT1, LAT2, PAT1, and PAT2 and whether the response is modified by development. Overnight fasted 6- and 26-day-old pigs were infused for 2 h with saline (Control) or with insulin or amino acids to achieve fed levels while amino acids or insulin, respectively, as well as glucose were maintained at fasting levels. The abundance of SNAT2, SNAT3, LAT1, LAT2, PAT1, and PAT2 was higher in muscle of 6- compared with 26-day-old pigs. The abundance of the PAT2–mTOR complex was greater in 6- than in 26-day-old pigs, consistent with the higher activation of mTORC1. Neither insulin nor amino acids altered amino acid transporter or PAT2–mTOR complex abundance. In conclusion, the amino acid transporters, SNAT 2/3, LAT 1/2, and PAT1/2, likely have important roles in the enhanced amino acidinduced activation of mTORC1 in skeletal muscle of the neonate.