Abstract
Background:
Sepsis induces loss of skeletal muscle mass by activating the ubiquitin proteasome (UPS) and autophagy systems. Although muscle protein synthesis in healthy neonatal piglets is responsive to amino acids (AA) stimulation, it is not known if AA can prevent the activation of muscle protein degradation induced by sepsis. We hypothesize that AA attenuate the sepsis-induced activation of UPS and autophagy in neonates.
Methods:
Newborn pigs were infused for 8 h with liposaccharide (LPS) (0 and 10 μg·kg−1·h−1), while circulating glucose and insulin were maintained at fasting levels; circulating AA were clamped at fasting or fed levels. Markers of protein degradation and AA transporters in longissimus dorsi (LD) were examined.
Results:
Fasting AA increased muscle microtubule-associated protein light 1 chain 3 II (LC3-II) abundance in LPS compared to control, while fed AA levels decreased LC3-II abundance in both LPS and controls. There was no effect of AA supplementation on activated protein kinase (AMP), forkhead box O1 and O4 phosphorylation, nor on sodium-coupled neutral AA transporter 2 and light chain AA transporter 1, muscle RING-finger protein-1 and muscle Atrophy F-Box/Atrogin-1 abundance.
Conclusion:
These findings suggest that supplementation of AA antagonize autophagy signal activation in skeletal muscle of neonates during endotoxemia.
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Acknowledgements
The authors thank Rosemarie Almonaci for technical support. This work is a publication of the U.S. Department of Agriculture/Agricultural Research Service 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 U.S. Department of Agriculture, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
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Hernandez-García, A., Manjarín, R., Suryawan, A. et al. Amino acids, independent of insulin, attenuate skeletal muscle autophagy in neonatal pigs during endotoxemia. Pediatr Res 80, 448–451 (2016). https://doi.org/10.1038/pr.2016.83
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DOI: https://doi.org/10.1038/pr.2016.83
