Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation

Abstract

Skeletal muscle in the neonate grows at a rapid rate due in part to an enhanced sensitivity to the postprandial rise in amino acids, particularly leucine. To elucidate the molecular mechanism by which leucine stimulates protein synthesis in neonatal muscle, overnight-fasted 7-day-old piglets were treated with rapamycin [an inhibitor of mammalian target of rapamycin (mTOR) complex (mTORC)1] for 1 h and then infused with leucine for 1 h. Fractional rates of protein synthesis and activation of signaling components that lead to mRNA translation were determined in skeletal muscle. Rapamycin completely blocked leucine-induced muscle protein synthesis. Rapamycin markedly reduced raptor-mTOR association, an indicator of mTORC1 activation. Rapamycin blocked the leucine-induced phosphorylation of mTOR, S6 kinase 1 (S6K1), and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1) and formation of the eIF4E.eIF4G complex and increased eIF4E.4E-BP1 complex abundance. Rapamycin had no effect on the association of mTOR with rictor, a crucial component for mTORC2 activation, or G protein beta-subunit-like protein (GbetaL), a component of mTORC1 and mTORC2. Neither leucine nor rapamycin affected the phosphorylation of AMP-activated protein kinase (AMPK), PKB, or tuberous sclerosis complex (TSC)2, signaling components that reside upstream of mTOR. Eukaryotic elongation factor (eEF)2 phosphorylation was not affected by leucine or rapamycin, although current dogma indicates that eEF2 phosphorylation is mTOR dependent. Together, these in vivo data suggest that leucine stimulates muscle protein synthesis in neonates by enhancing mTORC1 activation and its downstream effectors.

Contraction intensity and feeding affect collagen and myofibrillar protein synthesis rates differently in human skeletal muscle

“…Similarly, we could not detect any elevated phosphorylation by feeding (Fig. 6, E and F), although Akt-Ser 473 by any means is known to be highly sensitive to feeding (35,56,90). Recently, it was demonstrated that a threshold of insulin/amino acid availability has to be obtained for Akt to be phosphorylated (44,45), which may not have been obtained by the intermittent feeding regimen (Tables 2 and 3).…”

Suppression of mTORC1 activation in acid-α-glucosidase-deficient cells and mice is ameliorated by leucine supplementation

“…WT or Pompe mice were fasted for 12 h and infused through an intravenous line with saline or leucine (30 mg·kg Ϫ1 ·min Ϫ1 ) for 1 h, then intraperitoneally injected with 1 U/kg insulin or saline for 30 min. These timeframes were chosen on the basis of previous studies examining insulin-and leucine-stimulated mTORC1 activation in skeletal muscle (24). Skeletal muscle was collected, snap-frozen, and stored at Ϫ80°C.…”

<b>Cuts of dairy-origin cattle fed mesquite pod meal in replacement of corn

“…One reason may be related to the premise of an important parameter for ruminants, according to Jorge et al (2008), which is the nutritional value of mesquite pod meal, that is, good bromatological composition, with a CP content of 9.4% and TDN higher than 70%, in addition to high DM digestibility. Suryawan et al (2008) reported that mesquite pod meal has a higher proportion of leucine when compared to corn, an essential amino that is at the heart of muscle protein synthesis. Moraes et al (2016) argued that the digestibility of nutrients was not affected by the replacement of corn for mesquite pod meal.…”

“…In this sense, it is worth highlighting the role of branched-chain amino acids (leucine, isoleucine and valine), with leucine being one of the main stimulators of protein synthesis in skeletal muscles (Suryawan et al, 2008), whose concentration in the mesquite pod accounts for 4.59% of all present amino acids (Zavala & González, 1997), concentration higher than that found in corn, of approximately 1.05%, based on dry matter (Agustini et al, 2015), as it is able to stimulate protein synthesis (Suryawan et al, 2008) and, when combined, boosts the increase in muscle growth through this amino acid (Wu, 2009). …”