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| Item Type: | Article |
|---|---|
| Title: | Proteomic and transcriptomic changes in hibernating grizzly bears reveal metabolic and signaling pathways that protect against muscle atrophy |
| Creators Name: | Mugahid, D.A. and Sengul, T.G. and You, X. and Wang, Y. and Steil, L. and Bergmann, N. and Radke, M.H. and Ofenbauer, A. and Gesell-Salazar, M. and Balogh, A. and Kempa, S. and Tursun, B. and Robbins, C.T. and Völker, U. and Chen, W. and Nelson, L. and Gotthardt, M. |
| Abstract: | Muscle atrophy is a physiological response to disuse and malnutrition, but hibernating bears are largely resistant to this phenomenon. Unlike other mammals, they efficiently reabsorb amino acids from urine, periodically activate muscle contraction, and their adipocytes differentially responds to insulin. The contribution of myocytes to the reduced atrophy remains largely unknown. Here we show how metabolism and atrophy signaling are regulated in skeletal muscle of hibernating grizzly bear. Metabolic modeling of proteomic changes suggests an autonomous increase of non-essential amino acids (NEAA) in muscle and treatment of differentiated myoblasts with NEAA is sufficient to induce hypertrophy. Our comparison of gene expression in hibernation versus muscle atrophy identified several genes differentially regulated during hibernation, including Pdk4 and Serpinf1. Their trophic effects extend to myoblasts from non-hibernating species (including C. elegans), as documented by a knockdown approach. Together, these changes reflect evolutionary favored adaptations that, once translated to the clinics, could help improve atrophy treatment. |
| Keywords: | Duplex Specific Nuclease, Skeletal Muscle, Ubiquitin Ligases, Disuse Atrophy, Winter Sleep, RNA-Seq, κ-B, Gene, Expression, Activation, Animals, Grizzly Bears, Mice |
| Source: | Scientific Reports |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Volume: | 9 |
| Number: | 1 |
| Page Range: | 19976 |
| Date: | 27 December 2019 |
| Additional Information: | Erratum in: Sci Rep 10(1): 4381. |
| Official Publication: | https://doi.org/10.1038/s41598-019-56007-8 |
| PubMed: | View item in PubMed |
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