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Leucine is a major regulator of muscle protein synthesis in neonates

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Abstract

Approximately 10 % of infants born in the United States are of low birth weight. Growth failure during the neonatal period is a common occurrence in low birth weight infants due to their inability to tolerate full feeds, concerns about advancing protein supply, and high nutrient requirements for growth. An improved understanding of the nutritional regulation of growth during this critical period of postnatal growth is vital for the development of strategies to improve lean gain. Past studies with animal models have demonstrated that muscle protein synthesis is increased substantially following a meal and that this increase is due to the postprandial rise in amino acids as well as insulin. Both amino acids and insulin act independently to stimulate protein synthesis in a mammalian target of rapamycin-dependent manner. Further studies have elucidated that leucine, in particular, and its metabolites, α-ketoisocaproic acid and β-hydroxy-β-methylbutyrate, have unique anabolic properties. Supplementation with leucine, provided either parenterally or enterally, has been shown to enhance muscle protein synthesis in neonatal pigs, making it an ideal candidate for stimulating growth of low birth weight infants.

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Abbreviations

4EBP1:

4E-binding protein 1

AA:

Amino acids

Akt/PKB:

Protein kinase B

BCAA:

Branched-chain amino acids

BOL:

Bolus fed

CON:

Continuously fed

CON+LEU:

Continuously fed and pulsed with leucine

eIF4E:

Eukaryotic initiation factor 4E

eIF4G:

Eukaryotic initiation factor 4G

HMB:

β-Hydroxy-β-methylbutyrate

KIC:

α-Ketoisocaproic acid

mTOR:

Mammalian target of rapamycin

S6:

Ribosomal protein S6

S6K1:

Ribosomal protein S6 kinase 1

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Acknowledgments

The work was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases Grants AR-044474 (Davis) and AR-46308 (Fiorotto), National Institute of Child Health and Human Development HD-072891 (Davis), United States Department of Agriculture National Institute of Agriculture grant 2013-67015-20438 (Davis), and by the USDA/ARS under Cooperative Agreement no. 6250-510000-055 (Davis). This work is a publication of the USDA, Agricultural Research Service (USDA/ARS) Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX. The contents of this publication do not necessarily reflect the views or politics of the USDA, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government.

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  1. Department of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Daniel A. Columbus, Marta L. Fiorotto & Teresa A. Davis

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  1. Daniel A. Columbus
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Correspondence to Teresa A. Davis.

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Columbus, D.A., Fiorotto, M.L. & Davis, T.A. Leucine is a major regulator of muscle protein synthesis in neonates. Amino Acids 47, 259–270 (2015). https://doi.org/10.1007/s00726-014-1866-0

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