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  • Basic Science Article
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Preterm birth alters the feeding-induced activation of Akt signaling in the muscle of neonatal piglets

Pediatric Research volume 93, pages 1891–1898 (2023)Cite this article

Abstract

Background

Postnatal lean mass accretion is commonly reduced in preterm infants. This study investigated mechanisms involved in the blunted feeding-induced activation of Akt in the skeletal muscle of preterm pigs that contributes to lower protein synthesis rates.

Methods

On day 3 following cesarean section, preterm and term piglets were fasted or fed an enteral meal. Activation of Akt signaling pathways in skeletal muscle was determined.

Results

Akt1 and Akt2, but not Akt3, phosphorylation were lower in the skeletal muscle of preterm than in term pigs (P < 0.05). Activation of Akt-positive regulators, PDK1 and mTORC2, but not FAK, were lower in preterm than in term (P < 0.05). The formation of Akt complexes with GAPDH and Hsp90 and the abundance of Ubl4A were lower in preterm than in term (P < 0.05). The abundance of Akt inhibitors, PHLPP and SHIP2, but not PTEN and IP6K1, were higher in preterm than in term pigs (P < 0.05). PP2A activation was inhibited by feeding in term but not in preterm pigs (P < 0.05).

Conclusions

Our results suggest that preterm birth impairs regulatory components involved in Akt activation, thereby limiting the anabolic response to feeding. This anabolic resistance likely contributes to the reduced lean accretion following preterm birth.

Impact

  • The Akt-mTORC1 pathway plays an important role in the regulation of skeletal muscle protein synthesis in neonates.

  • This is the first evidence to demonstrate that, following preterm birth, the postprandial activation of positive regulators of Akt in the skeletal muscle is reduced, whereas the activation of negative regulators of Akt is enhanced.

  • This anabolic resistance of Akt signaling in response to feeding likely contributes to the reduced accretion of lean mass in premature infants.

  • These results may provide potential novel molecular targets for intervention to enhance lean growth in preterm neonates.

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Fig. 1: Current models of Akt activation.
Fig. 2: Preterm birth attenuates the phosphorylation of Akt1 and Akt2, but not Akt3.
Fig. 3: Preterm birth blunts positive regulators of Akt activation.
Fig. 4: Preterm birth upregulates Akt endogenous inhibitors.

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Data availability

The datasets supporting the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work is a publication of the USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine. The contents of this publication do not necessarily reflect the views or policies of the USDA, nor does the mention of trade names, commercial products, or organization imply endorsement by the US government. We thank H.V. Nguyen and R.D. Parada for expert technical assistance and the staff of the Comparative Nutrition Research Facility for animal care.

Funding

This work was supported by the National Institute of Child Health and Human Development Grants HD-085573 (T.A.D.), HD-072891 (T.A.D.), HD-099080 (T.A.D. and M.L.F.), USDA Current Research Information System Grant 3092-51000-060 (T.A.D.), and USDA National Institute of Food and Agriculture Grant 2013-67015-20438 (T.A.D.).

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Authors and Affiliations

  1. United States Department of Agriculture/Agricultural Research Service, Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA

    Agus Suryawan, Jane K. Naberhuis, Marta L. Fiorotto & Teresa A. Davis

  2. Department of Animal Sciences, Auburn University, Auburn, AL, 36849, USA

    Marko Rudar

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Contributions

A.S., M.L.F., and T.A.D. conceived and designed the research; A.S., M.R., and J.K.N. performed experiments; A.S. and M.R. analyzed data; A.S., M.R., J.K.N., and M.L.F. interpreted the results of experiments; A.S. drafted the manuscript; A.S., M.R., J.K.N., M.L.F., and T.A.D. edited and revised the manuscript; A.S., M.R., J.K.N., M.L.F., and T.A.D. approved the final version to be published.

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Correspondence to Teresa A. Davis.

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Suryawan, A., Rudar, M., Naberhuis, J.K. et al. Preterm birth alters the feeding-induced activation of Akt signaling in the muscle of neonatal piglets. Pediatr Res 93, 1891–1898 (2023). https://doi.org/10.1038/s41390-022-02382-4

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