Acute vs chronic hypoxia: what are the consequences for skeletal muscle mass?

Louise Deldicque, Marc Francaux

Abstract


Hypoxia is a state of lowered oxygen tension that can be created by environmental or pathological conditions. Regardless the origin of hypoxia, skeletal muscle cells adapt to deal with the acute or chronic reduction in oxygen availability. Although contrasting results have been reported as well, long lasting hypoxia generally leads to a negative regulation of protein balance and a loss of muscle mass whereas intermittent hypoxia seems rather to exert a positive effect on muscle growth in the context of a resistance exercise training. The purpose of the present review is to present the idea that chronic and acute hypoxia regulate skeletal muscle mass in two opposite ways. Chronic hypoxia-induced muscle atrophy in native highlanders, climbers or patients suffering from chronic obstructive pulmonary disease was previously thought to be caused by less calories ingestion and a reduced physical activity. More and more evidence accumulate showing that hypoxia itself contribute to the loss of muscle mass during chronic hypoxia. In contrast repeated acute hypoxic sessions have the potential to slow down muscle atrophy and even to stimulate muscle mass accretion when coupled to resistance exercise as it is the case with occlusion training. Further investigation should now focus on the molecular mechanisms by which acute and chronic hypoxia regulate skeletal muscle mass. A particular attention should be paid to satellite cells, which can be activated by hypoxia in vitro.

Keywords


protein synthesis; protein degradation; COPD; signalling; occlusion training

References


Abe T, Kearns CF, Sato Y (2006). Muscle size and strength are increased following walk training with restricted venous blood flow from the leg muscle, Kaatsu-walk training. J Appl Physiol 100:1460-1466.

Abe T, Sakamaki M, Fujita S, Ozaki H, Sugaya M, Sato Y, Nakajima T (2010). Effects of low-intensity walk training with restricted leg blood flow on muscle strength and aerobic capacity in older adults. J Geriatr Phys Ther 33:34-40.

Ameln H, Gustafsson T, Sundberg CJ, Okamoto K, Jansson E, Poellinger L, Makino Y (2005). Physiological activation of hypoxia inducible factor-1 in human skeletal muscle. FASEB J 19:1009-1011.

Arsham AM, Howell JJ, Simon MC (2003). A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets. J Biol Chem 278:29655-29660.

Baldi S, Aquilani R, Pinna GD, Poggi P, De Martini A, Bruschi C (2010). Fat-free mass change after nutritional rehabilitation in weight losing COPD: role of insulin, C-reactive protein and tissue hypoxia. Int J Chron Obstruct Pulmon Dis 5:29-39.

Bernard S, Leblanc P, Whittom F, Carrier G, Jobin J, Belleau R, Maltais F (1998). Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 158:629-634.

Bigard AX, Douce P, Merino D, Lienhard F, Guezennec CY (1996). Changes in dietary protein intake fail to prevent decrease in muscle growth induced by severe hypoxia in rats. J Appl Physiol 80:208-215.

Bonaldo P, Sandri M (2013). Cellular and molecular mechanisms of muscle atrophy. Dis Model Mech 6:25-39.

Brack AS, Conboy IM, Conboy MJ, Shen J, Rando TA (2008). A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis. Cell Stem Cell 2:50-59.

Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG, Jr. (2004). Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 18:2893-2904.

Cam H, Easton JB, High A, Houghton PJ (2010). mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1alpha. Mol Cell 40:509-520.

Cassano M, Quattrocelli M, Crippa S, Perini I, Ronzoni F, Sampaolesi M (2009). Cellular mechanisms and local progenitor activation to regulate skeletal muscle mass. J Muscle Res Cell Motil 30:243-253.

Chaillou T, Koulmann N, Meunier A, Malgoyre A, Serrurier B, Beaudry M, Bigard X (2013). Effect of hypoxia exposure on the phenotypic adaptation in remodelling skeletal muscle submitted to functional overload. Acta Physiol (Oxf).

Chaillou T, Koulmann N, Simler N, Meunier A, Serrurier B, Chapot R, Peinnequin A, Beaudry M, Bigard X (2012). Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model. Am J Physiol Regul Integr Comp Physiol 302:R643-R654.

Chaudhary P, Suryakumar G, Prasad R, Singh SN, Ali S, Ilavazhagan G (2012). Chronic hypobaric hypoxia mediated skeletal muscle atrophy: role of ubiquitin-proteasome pathway and calpains. Mol Cell Biochem 364:101-113.

Csete M, Walikonis J, Slawny N, Wei Y, Korsnes S, Doyle JC, Wold B (2001). Oxygen-mediated regulation of skeletal muscle satellite cell proliferation and adipogenesis in culture. J Cell Physiol 189:189-196.

D'Hulst G, Jamart C, Van TR, Hespel P, Francaux M, Deldicque L (2013). Effect of acute environmental hypoxia on protein metabolism in human skeletal muscle. Acta Physiol (Oxf) 208:251-264.

De Palma S, Ripamonti M, Vigano A, Moriggi M, Capitanio D, Samaja M, Milano G, Cerretelli P, Wait R, Gelfi C (2007). Metabolic modulation induced by chronic hypoxia in rats using a comparative proteomic analysis of skeletal muscle tissue. J Proteome Res 6:1974-1984.

Debigare R, Cote CH, Maltais F (2001). Peripheral muscle wasting in chronic obstructive pulmonary disease. Clinical relevance and mechanisms. Am J Respir Crit Care Med 164:1712-1717.

Debigare R, Marquis K, Cote CH, Tremblay RR, Michaud A, Leblanc P, Maltais F (2003). Catabolic/anabolic balance and muscle wasting in patients with COPD. Chest 124:83-89.

Drummond MJ, Fujita S, Abe T, Dreyer HC, Volpi E, Rasmussen BB (2008). Human muscle gene expression following resistance exercise and blood flow restriction. Med Sci Sports Exerc 40:691-698.

Etheridge T, Atherton PJ, Wilkinson D, Selby A, Rankin D, Webborn N, Smith K, Watt PW (2011). Effects of hypoxia on muscle protein synthesis and anabolic signaling at rest and in response to acute resistance exercise. Am J Physiol Endocrinol Metab 301:E697-E702.

Favier FB, Costes F, Defour A, Bonnefoy R, Lefai E, Bauge S, Peinnequin A, Benoit H, Freyssenet D (2010). Downregulation of Akt/mammalian target of rapamycin pathway in skeletal muscle is associated with increased REDD1 expression in response to chronic hypoxia. Am J Physiol Regul Integr Comp Physiol 298:R1659-R1666.

Fiori G, Facchini F, Ismagulov O, Ismagulova A, Tarazona-Santos E, Pettener D (2000). Lung volume, chest size, and hematological variation in low-, medium-, and high-altitude central Asian populations. Am J Phys Anthropol 113:47-59.

Friedmann B, Kinscherf R, Borisch S, Richter G, Bartsch P, Billeter R (2003). Effects of low-resistance/high-repetition strength training in hypoxia on muscle structure and gene expression. Pflugers Arch 446:742-751.

Fry CS, Glynn EL, Drummond MJ, Timmerman KL, Fujita S, Abe T, Dhanani S, Volpi E, Rasmussen BB (2010). Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older men. J Appl Physiol 108:1199-1209.

Fujita S, Abe T, Drummond MJ, Cadenas JG, Dreyer HC, Sato Y, Volpi E, Rasmussen BB (2007). Blood flow restriction during low-intensity resistance exercise increases S6K1 phosphorylation and muscle protein synthesis. J Appl Physiol 103:903-910.

Garvey JF, Taylor CT, McNicholas WT (2009). Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation. Eur Respir J 33:1195-1205.

Gentil P, Oliveira E, Bottaro M (2006). Time under tension and blood lactate response during four different resistance training methods. J Physiol Anthropol 25:339-344.

Gosker HR, Engelen MP, van MH, van Dijk PJ, van der Vusse GJ, Wouters EF, Schols AM (2002). Muscle fiber type IIX atrophy is involved in the loss of fat-free mass in chronic obstructive pulmonary disease. Am J Clin Nutr 76:113-119.

Green H, Roy B, Grant S, Burnett M, Tupling R, Otto C, Pipe A, McKenzie D (2000). Downregulation in muscle Na(+)-K(+)-ATPase following a 21-day expedition to 6,194 m. J Appl Physiol 88:634-640.

Greer SN, Metcalf JL, Wang Y, Ohh M (2012). The updated biology of hypoxia-inducible factor. EMBO J 31:2448-2460.

Grocott M, Montgomery H, Vercueil A (2007). High-altitude physiology and pathophysiology: implications and relevance for intensive care medicine. Crit Care 11:203.

Holm L, Haslund ML, Robach P, van HG, Calbet JA, Saltin B, Lundby C (2010). Skeletal muscle myofibrillar and sarcoplasmic protein synthesis rates are affected differently by altitude-induced hypoxia in native lowlanders. PLoS One 5:e15606.

Hoppeler H, Kleinert E, Schlegel C, Claassen H, Howald H, Kayar SR, Cerretelli P (1990). Morphological adaptations of human skeletal muscle to chronic hypoxia. Int J Sports Med 11 Suppl 1:S3-S9.

Hussain SN, Sandri M (2013). Role of autophagy in COPD skeletal muscle dysfunction. J Appl Physiol 114:1273-1281.

Imoberdorf R, Garlick PJ, McNurlan MA, Casella GA, Marini JC, Turgay M, Bartsch P, Ballmer PE (2006). Skeletal muscle protein synthesis after active or passive ascent to high altitude. Med Sci Sports Exerc 38:1082-1087.

Jagoe RT, Engelen MP (2003). Muscle wasting and changes in muscle protein metabolism in chronic obstructive pulmonary disease. Eur Respir J Suppl 46:52s-63s.

Jobin J, Maltais F, Doyon JF, Leblanc P, Simard PM, Simard AA, Simard C (1998). Chronic obstructive pulmonary disease: capillarity and fiber-type characteristics of skeletal muscle. J Cardiopulm Rehabil 18:432-437.

Kawada S, Ishii N (2005). Skeletal muscle hypertrophy after chronic restriction of venous blood flow in rats. Med Sci Sports Exerc 37:1144-1150.

Kawada S, Ishii N (2008). Changes in skeletal muscle size, fibre-type composition and capillary supply after chronic venous occlusion in rats. Acta Physiol (Oxf) 192:541-549.

Kayser B (1994). Nutrition and energetics of exercise at altitude. Theory and possible practical implications. Sports Med 17:309-323.

Koning M, Werker PM, van Luyn MJ, Harmsen MC (2011). Hypoxia promotes proliferation of human myogenic satellite cells: a potential benefactor in tissue engineering of skeletal muscle. Tissue Eng Part A 17:1747-1758.

Koritzinsky M, Magagnin MG, van den Beucken T, Seigneuric R, Savelkouls K, Dostie J, Pyronnet S, Kaufman RJ, Weppler SA, Voncken JW, Lambin P, Koumenis C, Sonenberg N, Wouters BG (2006). Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control. EMBO J 25:1114-1125.

Koumenis C, Wouters BG (2006). "Translating" tumor hypoxia: unfolded protein response (UPR)-dependent and UPR-independent pathways. Mol Cancer Res 4:423-436.

Lacey RJ, Cable HC, James RF, London NJ, Scarpello JH, Morgan NG (1993). Concentration-dependent effects of adrenaline on the profile of insulin secretion from isolated human islets of Langerhans. J Endocrinol 138:555-563.

Larsen JJ, Hansen JM, Olsen NV, Galbo H, Dela F (1997). The effect of altitude hypoxia on glucose homeostasis in men. J Physiol 504 ( Pt 1):241-249.

Laurentino GC, Ugrinowitsch C, Roschel H, Aoki MS, Soares AG, Neves M, Jr., Aihara AY, Fernandes AR, Tricoli V (2012). Strength training with blood flow restriction diminishes myostatin gene expression. Med Sci Sports Exerc 44:406-412.

Lee WH, Kim YW, Choi JH, Brooks SC, III, Lee MO, Kim SG (2009). Oltipraz and dithiolethione congeners inhibit hypoxia-inducible factor-1alpha activity through p70 ribosomal S6 kinase-1 inhibition and H2O2-scavenging effect. Mol Cancer Ther 8:2791-2802.

Liu L, Cash TP, Jones RG, Keith B, Thompson CB, Simon MC (2006). Hypoxia-induced energy stress regulates mRNA translation and cell growth. Mol Cell 21:521-531.

Loenneke JP, Kearney ML, Thrower AD, Collins S, Pujol TJ (2010). The acute response of practical occlusion in the knee extensors. J Strength Cond Res 24:2831-2834.

Loenneke JP, Wilson JM, Marin PJ, Zourdos MC, Bemben MG (2012). Low intensity blood flow restriction training: a meta-analysis. Eur J Appl Physiol 112:1849-1859.

Lundby C, Pilegaard H, Andersen JL, van HG, Sander M, Calbet JA (2004). Acclimatization to 4100 m does not change capillary density or mRNA expression of potential angiogenesis regulatory factors in human skeletal muscle. J Exp Biol 207:3865-3871.

Macaluso F, Myburgh KH (2012). Current evidence that exercise can increase the number of adult stem cells. J Muscle Res Cell Motil 33:187-198.

MacDougall JD, Green HJ, Sutton JR, Coates G, Cymerman A, Young P, Houston CS (1991). Operation Everest II: structural adaptations in skeletal muscle in response to extreme simulated altitude. Acta Physiol Scand 142:421-427.

Manini TM, Vincent KR, Leeuwenburgh CL, Lees HA, Kavazis AN, Borst SE, Clark BC (2011). Myogenic and proteolytic mRNA expression following blood flow restricted exercise. Acta Physiol (Oxf) 201:255-263.

Martinelli M, Winterhalder R, Cerretelli P, Howald H, Hoppeler H (1990). Muscle lipofuscin content and satellite cell volume is increased after high altitude exposure in humans. Experientia 46:672-676.

Mazzeo RS, Wolfel EE, Butterfield GE, Reeves JT (1994). Sympathetic response during 21 days at high altitude (4,300 m) as determined by urinary and arterial catecholamines. Metabolism 43:1226-1232.

Millet GP, Faiss R, Pialoux V (2012). Point: Hypobaric hypoxia induces different physiological responses from normobaric hypoxia. J Appl Physiol 112:1783-1784.

Mizuno M, Savard GK, Areskog NH, Lundby C, Saltin B (2008). Skeletal muscle adaptations to prolonged exposure to extreme altitude: a role of physical activity? High Alt Med Biol 9:311-317.

Nielsen JL, Aagaard P, Bech RD, Nygaard T, Hvid LG, Wernbom M, Suetta C, Frandsen U (2012). Proliferation of myogenic stem cells in human skeletal muscle in response to low-load resistance training with blood flow restriction. J Physiol 590:4351-4361.

Nishimura A, Sugita M, Kato K, Fukuda A, Sudo A, Uchida A (2010). Hypoxia increases muscle hypertrophy induced by resistance training. Int J Sports Physiol Perform 5:497-508.

Pallafacchina G, Blaauw B, Schiaffino S (2012). Role of satellite cells in muscle growth and maintenance of muscle mass. Nutr Metab Cardiovasc Dis.

Plant PJ, Brooks D, Faughnan M, Bayley T, Bain J, Singer L, Correa J, Pearce D, Binnie M, Batt J (2010). Cellular markers of muscle atrophy in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 42:461-471.

Raguso CA, Guinot SL, Janssens JP, Kayser B, Pichard C (2004). Chronic hypoxia: common traits between chronic obstructive pulmonary disease and altitude. Curr Opin Clin Nutr Metab Care 7:411-417.

Rennie MJ (2003). Claims for the anabolic effects of growth hormone: a case of the emperor's new clothes? Br J Sports Med 37:100-105.

Rennie MJ, Babij P, Sutton JR, Tonkins WJ, Read WW, Ford C, Halliday D (1983). Effects of acute hypoxia on forearm leucine metabolism. Prog Clin Biol Res 136:317-323.

Rose MS, Houston CS, Fulco CS, Coates G, Sutton JR, Cymerman A (1988). Operation Everest. II: Nutrition and body composition. J Appl Physiol 65:2545-2551.

Sawhney RC, Malhotra AS, Singh T (1991). Glucoregulatory hormones in man at high altitude. Eur J Appl Physiol Occup Physiol 62:286-291.

Schols AM, Broekhuizen R, Weling-Scheepers CA, Wouters EF (2005). Body composition and mortality in chronic obstructive pulmonary disease. Am J Clin Nutr 82:53-59.

Semenza GL (2011). Regulation of metabolism by hypoxia-inducible factor 1. Cold Spring Harb Symp Quant Biol 76:347-353.

Sumide T, Sakuraba K, Sawaki K, Ohmura H, Tamura Y (2009). Effect of resistance exercise training combined with relatively low vascular occlusion. J Sci Med Sport 12:107-112.

Takano H, Morita T, Iida H, Asada K, Kato M, Uno K, Hirose K, Matsumoto A, Takenaka K, Hirata Y, Eto F, Nagai R, Sato Y, Nakajima T (2005). Hemodynamic and hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle blood flow. Eur J Appl Physiol 95:65-73.

Takarada Y, Nakamura Y, Aruga S, Onda T, Miyazaki S, Ishii N (2000a). Rapid increase in plasma growth hormone after low-intensity resistance exercise with vascular occlusion. J Appl Physiol 88:61-65.

Takarada Y, Takazawa H, Ishii N (2000b). Applications of vascular occlusion diminish disuse atrophy of knee extensor muscles. Med Sci Sports Exerc 32:2035-2039.

Tanida I (2011). Autophagosome formation and molecular mechanism of autophagy. Antioxid Redox Signal 14:2201-2214.

Urbani L, Piccoli M, Franzin C, Pozzobon M, De CP (2012). Hypoxia increases mouse satellite cell clone proliferation maintaining both in vitro and in vivo heterogeneity and myogenic potential. PLoS One 7:e49860.

Victor RG, Seals DR (1989). Reflex stimulation of sympathetic outflow during rhythmic exercise in humans. Am J Physiol 257:H2017-H2024.

Vigano A, Ripamonti M, De PS, Capitanio D, Vasso M, Wait R, Lundby C, Cerretelli P, Gelfi C (2008). Proteins modulation in human skeletal muscle in the early phase of adaptation to hypobaric hypoxia. Proteomics 8:4668-4679.

Whittom F, Jobin J, Simard PM, Leblanc P, Simard C, Bernard S, Belleau R, Maltais F (1998). Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. Med Sci Sports Exerc 30:1467-1474.

Wood SC, Stabenau EK (1998). Effect of gender on thermoregulation and survival of hypoxic rats. Clin Exp Pharmacol Physiol 25:155-158.


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Cell Mol Exerc Physiol (CMEP) Online ISSN: 2049-419X Prefix DOI: 10.7457