title: 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.
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 consequeces 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.
authors: School of Biological Sciences, University of Reading, Whiteknights campus, Reading, United Kingdom.
authors: Henry
authors: H
authors: Collins-Hooper
authors: Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy.
authors: Roberta
authors: R
authors: Sartori
authors: Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights campus, Reading, United Kingdom.
authors: Natasa
authors: N
authors: Giallourou
authors: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Hull/York, United Kingdom.
authors: Antonios
authors: A
authors: Matsakas
authors: School of Biological Sciences, University of Reading, Whiteknights campus, Reading, United Kingdom.
authors: Robert
authors: R
authors: Mitchell
authors: Helen P
authors: HP
authors: Makarenkova
authors: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
authors: Helen
authors: H
authors: Mararenkova
authors: School of Biological Sciences, University of Reading, Whiteknights campus, Reading, United Kingdom.
authors: Hannah
authors: H
authors: Flasskamp
authors: Veterinary Basic Sciences, Royal Veterinary College, London, United Kingdom.
authors: Raymond
authors: R
authors: Macharia
authors: Natural Biosciences, University of Reading, Whiteknights campus, Reading, United Kingdom.
authors: Steve
authors: S
authors: Ray
authors: Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights campus, Reading, United Kingdom.
authors: Jonathan R
authors: JR
authors: Swann
authors: Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy.
authors: Marco
authors: M
authors: Sandri
authors: School of Biological Sciences, University of Reading, Whiteknights campus, Reading, United Kingdom.
authors: Ketan
authors: K
authors: Patel
mesh_terms: D000818:Animals; D001343:Autophagy; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D017874:Immediate-Early Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D055442:Metabolome; D051379:Mice; D018345:Mice, Knockout; D009129:Muscle Tonus; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D055435:Myostatin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D059748:Proteolysis; D060888:Real-Time Polymerase Chain Reaction; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D017874:Immediate-Early Proteins; D055435:Myostatin; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C525912:Mstn protein, mouse