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Ethanol acutely antagonizes the refeeding-induced increase in mTOR-dependent protein synthesis and decrease in autophagy in skeletal muscle

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Abstract

The purpose of this study was to determine the impact of acute ethanol administration on the major signal transduction pathways in skeletal muscle responsible for regulating the protein synthetic and degradative response to refeeding. Adult male C57Bl/6 mice were fasted overnight; mice were then either refed normal rodent chow for 30 min or a separate group of mice remained food deprived (i.e., fasted). Thereafter, mice were administered either 3 g/kg ethanol or saline. Gastrocnemius/plantaris was collected 1 h later and analyzed. Acute ethanol decreased basal and prevented the refeeding-induced increase in muscle protein synthesis. While ethanol prevented a nutrient-stimulated increase in S6K1 phosphorylation, it did not alter the increase in 4E-BP1 phosphorylation. Downstream of S6K1, ethanol also attenuated the refeeding-induced increase in S6 and eIF4B phosphorylation, as well as the decrease in eEF2 phosphorylation. Although ethanol decreased ERK and p90 RSK phosphorylation, activation of this signaling pathway was not altered by refeeding in either control or ethanol-treated mice. Related to protein degradation, in vitro-determined proteasome activity and the content of total ubiquitinated proteins were not altered by ethanol and/or refeeding. Control mice appeared to exhibit a refeeding-induced decrease in autophagy as suggested by the increased FoxO3 and ULK1 phosphorylation and total p62 protein as well as decreased LC3B-II; however, ethanol blunted these refeeding-induced changes. These data suggest that ethanol can acutely prevent the normally observed mTOR-dependent increase in protein synthesis and reduction in autophagy in response to nutrient stimulation, but does not appear to acutely alter proteasome activity.

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Acknowledgements

The authors would like to acknowledge the expert technical assistance of Anne Pruznak and Maithili Navarantnarajah. Research reported in this publication was supported by the National Institutes of Health under Award Numbers R37 AA011290 (CHL) and F32 AA023422 (JLS).

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  1. Jennifer L. Steiner

    Present address: Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, 32306, USA

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  1. Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA, 17033, USA

    Jennifer L. Steiner & Charles H. Lang

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Correspondence to Charles H. Lang.

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Steiner, J.L., Lang, C.H. Ethanol acutely antagonizes the refeeding-induced increase in mTOR-dependent protein synthesis and decrease in autophagy in skeletal muscle. Mol Cell Biochem 456, 41–51 (2019). https://doi.org/10.1007/s11010-018-3488-4

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  • DOI: https://doi.org/10.1007/s11010-018-3488-4

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