Abundance of amino acid transporters involved in mTORC1 activation in skeletal muscle of neonatal pigs is developmentally regulated.
Previously we demonstrated that the insulin- and 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 post-prandial 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 acid-induced activation of mTORC1 in skeletal muscle of the neonate.
Department of Pediatrics and United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA.
Agus
A
Suryawan
Hanh V
HV
Nguyen
Rosemarie D
RD
Almonaci
Teresa A
TA
Davis
D026905:Amino Acid Transport Systems / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D018507:Gene Expression Regulation, Developmental; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D013552:Swine; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D026905:Amino Acid Transport Systems; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases