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
Jonathan R. Swann
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.
|Journal Article Type||Article|
|Publication Date||Mar 25, 2015|
|Publisher||Public Library of Science|
|Peer Reviewed||Peer Reviewed|
|Article Number||ARTN e0120524|
|Institution Citation||Collins-Hooper, H., Sartori, R., Giallourou, N., Matsakas, A., Mitchell, R., Mararenkova, H., …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. doi:10.1371/journal.pone.0120524|
|Keywords||Muscle protein synthesis, Starvation, Muscle biochemistry|
|Copyright Statement||© 2015 Collins-Hooper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Additional Information||Copy of article first published in: PLoS ONE 2015, 10(3): e0120524.|
© 2015 Collins-Hooper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.