Symmorphosis through dietary regulation: A combinatorial role for proteolysis, autophagy and protein synthesis in normalising muscle metabolism and function of hypertrophic mice after acute starvation

Collins-Hooper, Henry; Sartori, Roberta; Giallourou, Natasa; Matsakas, Antonios; Mitchell, Robert; Mararenkova, Helen; Flasskamp, Hannah; Macharia, Raymond; Ray, Steve; Swann, Jonathan R.; Sandri, Marco; Patel, Ketan

Abstract

Animals are imbued with adaptive mechanisms spanning from the tissue/organ to the cellular scale which insure that processes of homeostasis are preserved in the landscape of size change. However we and others have postulated that the degree of adaptation is limited and that once outside the normal levels of size fluctuations, cells and tissues function in an aberant manner. In this study we examine the function of muscle in the myostatin null mouse which is an excellent model for hypertrophy beyond levels of normal growth and consequences of acute starvation to restore mass. We show that muscle growth is sustained through protein synthesis driven by Serum/Glucocorticoid Kinase 1 (SGK1) rather than Akt1. Furthermore our metabonomic profiling of hypertrophic muscle shows that carbon from nutrient sources is being channelled for the production of biomass rather than ATP production. However the muscle displays elevated levels of autophagy and decreased levels of muscle tension. We demonstrate the myostatin null muscle is acutely sensitive to changes in diet and activates both the proteolytic and autophagy programmes and shutting down protein synthesis more extensively than is the case for wild-types. Poignantly we show that acute starvation which is detrimental to wild-type animals is beneficial in terms of metabolism and muscle function in the myostatin null mice by normalising tension production.

Citation

Collins-Hooper, H., Sartori, R., Giallourou, N., Matsakas, A., Mitchell, R., Mararenkova, H., Flasskamp, H., Macharia, R., Ray, S., Swann, J. R., Sandri, M., & Patel, K. (2015). Symmorphosis through dietary regulation: A combinatorial role for proteolysis, autophagy and protein synthesis in normalising muscle metabolism and function of hypertrophic mice after acute starvation. PLoS ONE, 10(3), e0120524. https://doi.org/10.1371/journal.pone.0120524

• Journal Article Type: Article
• Acceptance Date: Feb 5, 2015
• Online Publication Date: Mar 25, 2015
• Publication Date: Mar 25, 2015
• Deposit Date: May 20, 2015
• Publicly Available Date: May 20, 2015
• Journal: PLoS ONE
• Print ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 3
• Article Number: ARTN e0120524
• Pages: e0120524
• DOI: https://doi.org/10.1371/journal.pone.0120524
• Keywords: Muscle protein synthesis, Starvation, Muscle biochemistry
• Public URL: https://hull-repository.worktribe.com/output/374090
• Publisher URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120524
• Additional Information: Copy of article first published in: PLoS ONE 2015, 10(3): e0120524.
• Contract Date: May 20, 2015