Exercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation

Cell Metabolism - Tập 17 Số 2 - Trang 162-184 - 2013
Brendan Egan1,2, Juleen R. Zierath1,3,4
1Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm SE-171 77, Sweden
2Institute for Sport and Health, School of Public Health, Physiotherapy and Population Science, University College Dublin, Belfield, Dublin 4, Ireland
3Department of Physiology and Pharmacology, Section of Integrative Physiology, Karolinska Institute, Stockholm SE-171 77, Sweden
4Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark

Tóm tắt

Từ khóa


Tài liệu tham khảo

Adams, 1998, Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats, J. Appl. Physiol., 84, 1716, 10.1152/jappl.1998.84.5.1716

Adams, 1993, Skeletal muscle myosin heavy chain composition and resistance training, J. Appl. Physiol., 74, 911, 10.1152/jappl.1993.74.2.911

Ahlborg, 1974, Substrate turnover during prolonged exercise in man. Splanchnic and leg metabolism of glucose, free fatty acids, and amino acids, J. Clin. Invest., 53, 1080, 10.1172/JCI107645

Akimoto, 2005, Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway, J. Biol. Chem., 280, 19587, 10.1074/jbc.M408862200

Allen, 1999, Myonuclear domains in muscle adaptation and disease, Muscle Nerve, 22, 1350, 10.1002/(SICI)1097-4598(199910)22:10<1350::AID-MUS3>3.0.CO;2-8

Ambros, 2004, The functions of animal microRNAs, Nature, 431, 350, 10.1038/nature02871

Ameln, 2005, Physiological activation of hypoxia inducible factor-1 in human skeletal muscle, FASEB J., 19, 1009, 10.1096/fj.04-2304fje

Andersen, 1985, Maximal perfusion of skeletal muscle in man, J. Physiol., 366, 233, 10.1113/jphysiol.1985.sp015794

Atherton, 2005, Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation, FASEB J., 19, 786, 10.1096/fj.04-2179fje

Baar, 1999, Phosphorylation of p70(S6k) correlates with increased skeletal muscle mass following resistance exercise, Am. J. Physiol., 276, C120, 10.1152/ajpcell.1999.276.1.C120

Baar, 2002, Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1, FASEB J., 16, 1879, 10.1096/fj.02-0367com

Babraj, 2009, Extremely short duration high intensity interval training substantially improves insulin action in young healthy males, BMC Endocr. Disord., 9, 3, 10.1186/1472-6823-9-3

Banerjee, 2005, Prolonged electrical muscle stimulation exercise improves strength and aerobic capacity in healthy sedentary adults, J. Appl. Physiol., 99, 2307, 10.1152/japplphysiol.00891.2004

Barrès, 2012, Acute exercise remodels promoter methylation in human skeletal muscle, Cell Metab., 15, 405, 10.1016/j.cmet.2012.01.001

Benziane, 2008, Divergent cell signaling after short-term intensified endurance training in human skeletal muscle, Am. J. Physiol. Endocrinol. Metab., 295, E1427, 10.1152/ajpendo.90428.2008

Bergeron, 2001, Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis, Am. J. Physiol. Endocrinol. Metab., 281, E1340, 10.1152/ajpendo.2001.281.6.E1340

Biolo, 1995, Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans, Am. J. Physiol., 268, E514

Bodine, 2001, Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo, Nat. Cell Biol., 3, 1014, 10.1038/ncb1101-1014

Bolster, 2002, AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling, J. Biol. Chem., 277, 23977, 10.1074/jbc.C200171200

Booth, 1977, Effects of endurance exercise on cytochrome C turnover in skeletal muscle, Ann. N Y Acad. Sci., 301, 431, 10.1111/j.1749-6632.1977.tb38219.x

Booth, 2009, Lack of adequate appreciation of physical exercise’s complexities can pre-empt appropriate design and interpretation in scientific discovery, J. Physiol., 587, 5527, 10.1113/jphysiol.2009.179507

Booth, 1991, Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models, Physiol. Rev., 71, 541, 10.1152/physrev.1991.71.2.541

Booth, 1997, Physical activity preferences, preferred sources of assistance, and perceived barriers to increased activity among physically inactive Australians, Prev. Med., 26, 131, 10.1006/pmed.1996.9982

Booth, 2010, Gold standards for scientists who are conducting animal-based exercise studies, J. Appl. Physiol., 108, 219, 10.1152/japplphysiol.00125.2009

Booth, 2012, Lack of exercise is a major cause of chronic disease, Comp. Physiol., 2, 1143, 10.1002/cphy.c110025

Børsheim, 2003, Effect of exercise intensity, duration and mode on post-exercise oxygen consumption, Sports Med., 33, 1037, 10.2165/00007256-200333140-00002

Borst, 2004, Interventions for sarcopenia and muscle weakness in older people, Age Ageing, 33, 548, 10.1093/ageing/afh201

Bortoluzzi, 2006, Computational reconstruction of the human skeletal muscle secretome, Proteins, 62, 776, 10.1002/prot.20803

Boström, 2012, A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis, Nature, 481, 463, 10.1038/nature10777

Bouchard, 2012, Genomic predictors of trainability, Exp. Physiol., 97, 347, 10.1113/expphysiol.2011.058735

Bouchard, 1999, Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study, J. Appl. Physiol., 87, 1003, 10.1152/jappl.1999.87.3.1003

Bouchard, 2012, Adverse metabolic response to regular exercise: is it a rare or common occurrence?, PLoS ONE, 7, e37887, 10.1371/journal.pone.0037887

Bouzakri, 2011, Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle, Diabetes, 60, 1111, 10.2337/db10-1178

Brooks, 1998, Mammalian fuel utilization during sustained exercise, Comp. Biochem. Physiol. B Biochem. Mol. Biol., 120, 89, 10.1016/S0305-0491(98)00025-X

Bua, 2002, Mitochondrial abnormalities are more frequent in muscles undergoing sarcopenia, J. Appl. Physiol., 92, 2617, 10.1152/japplphysiol.01102.2001

Burgomaster, 2008, Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans, J. Physiol., 586, 151, 10.1113/jphysiol.2007.142109

Calvo, 2008, Muscle-specific expression of PPARgamma coactivator-1alpha improves exercise performance and increases peak oxygen uptake, J. Appl. Physiol., 104, 1304, 10.1152/japplphysiol.01231.2007

Cantó, 2009, AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity, Nature, 458, 1056, 10.1038/nature07813

Carey, 2009, Novel pharmacological approaches to combat obesity and insulin resistance: targeting skeletal muscle with ‘exercise mimetics’, Diabetologia, 52, 2015, 10.1007/s00125-009-1420-x

Carling, 1989, The substrate and sequence specificity of the AMP-activated protein kinase. Phosphorylation of glycogen synthase and phosphorylase kinase, Biochim. Biophys. Acta, 1012, 81, 10.1016/0167-4889(89)90014-1

Cartoni, 2005, Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise, J. Physiol., 567, 349, 10.1113/jphysiol.2005.092031

Chin, 2010, Intracellular Ca2+ signaling in skeletal muscle: decoding a complex message, Exerc. Sport Sci. Rev., 38, 76, 10.1097/JES.0b013e3181d495d2

Chinsomboon, 2009, The transcriptional coactivator PGC-1alpha mediates exercise-induced angiogenesis in skeletal muscle, Proc. Natl. Acad. Sci. USA, 106, 21401, 10.1073/pnas.0909131106

Choi, 2008, Paradoxical effects of increased expression of PGC-1alpha on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism, Proc. Natl. Acad. Sci. USA, 105, 19926, 10.1073/pnas.0810339105

Clarke, 2007, The E3 Ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscle, Cell Metab., 6, 376, 10.1016/j.cmet.2007.09.009

Coffey, 2007, The molecular bases of training adaptation, Sports Med., 37, 737, 10.2165/00007256-200737090-00001

Coffey, 2006, Interaction of contractile activity and training history on mRNA abundance in skeletal muscle from trained athletes, Am. J. Physiol. Endocrinol. Metab., 290, E849, 10.1152/ajpendo.00299.2005

Coffey, 2006, Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans, FASEB J., 20, 190, 10.1096/fj.05-4809fje

Colberg, 2010, Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement, Diabetes Care, 33, e147, 10.2337/dc10-9990

Davidsen, 2011, High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression, J. Appl. Physiol., 110, 309, 10.1152/japplphysiol.00901.2010

Davidson, 2009, Effects of exercise modality on insulin resistance and functional limitation in older adults: a randomized controlled trial, Arch. Intern. Med., 169, 122, 10.1001/archinternmed.2008.558

De Filippis, 2008, Insulin-resistant muscle is exercise resistant: evidence for reduced response of nuclear-encoded mitochondrial genes to exercise, Am. J. Physiol. Endocrinol. Metab., 294, E607, 10.1152/ajpendo.00729.2007

DeFronzo, 1981, The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization, Diabetes, 30, 1000, 10.2337/diab.30.12.1000

Dolmetsch, 1997, Differential activation of transcription factors induced by Ca2+ response amplitude and duration, Nature, 386, 855, 10.1038/386855a0

Dudley, 1987, Influence of mitochondrial content on the sensitivity of respiratory control, J. Biol. Chem., 262, 9109, 10.1016/S0021-9258(18)48054-4

Durieux, 2009, Focal adhesion kinase is a load-dependent governor of the slow contractile and oxidative muscle phenotype, J. Physiol., 587, 3703, 10.1113/jphysiol.2009.171355

Egan, 2010, Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor coactivator-1 mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle, J. Physiol., 588, 1779, 10.1113/jphysiol.2010.188011

Egan, 2011, 2-D DIGE analysis of the mitochondrial proteome from human skeletal muscle reveals time course-dependent remodelling in response to 14 consecutive days of endurance exercise training, Proteomics, 11, 1413, 10.1002/pmic.201000597

Ellingsgaard, 2011, Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells, Nat. Med., 17, 1481, 10.1038/nm.2513

Essig, 1996, Contractile activity-induced mitochondrial biogenesis in skeletal muscle, Exerc. Sport Sci. Rev., 24, 289, 10.1249/00003677-199600240-00012

Fang, 2001, Phosphatidic acid-mediated mitogenic activation of mTOR signaling, Science, 294, 1942, 10.1126/science.1066015

Flück, 2003, Molecular basis of skeletal muscle plasticity—from gene to form and function, Rev. Physiol. Biochem. Pharmacol., 146, 159, 10.1007/s10254-002-0004-7

Folland, 2007, The adaptations to strength training : morphological and neurological contributions to increased strength, Sports Med., 37, 145, 10.2165/00007256-200737020-00004

Formenti, 2010, Regulation of human metabolism by hypoxia-inducible factor, Proc. Natl. Acad. Sci. USA, 107, 12722, 10.1073/pnas.1002339107

Gaitanos, 1993, Human muscle metabolism during intermittent maximal exercise, J. Appl. Physiol., 75, 712, 10.1152/jappl.1993.75.2.712

Galbo, 1983

Garcia-Roves, 2008, Gain-of-function R225Q mutation in AMP-activated protein kinase gamma3 subunit increases mitochondrial biogenesis in glycolytic skeletal muscle, J. Biol. Chem., 283, 35724, 10.1074/jbc.M805078200

Garland, 2011, The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives, J. Exp. Biol., 214, 206, 10.1242/jeb.048397

Gavin, 2007, No difference in the skeletal muscle angiogenic response to aerobic exercise training between young and aged men, J. Physiol., 585, 231, 10.1113/jphysiol.2007.143198

Geng, 2010, PGC-1alpha plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle, Am. J. Physiol. Cell Physiol., 298, C572, 10.1152/ajpcell.00481.2009

Gerhart-Hines, 2007, Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha, EMBO J., 26, 1913, 10.1038/sj.emboj.7601633

Gibala, 2006, Effect of exercise on skeletal muscle protein and amino acid metabolism in humans, 137

Gibala, 1998, Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise, Am. J. Physiol., 275, E235

Glund, 2007, Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle, Diabetes, 56, 1630, 10.2337/db06-1733

Goldstein, 1961, Humoral nature of hypoglycemia in muscular exercise, Am. J. Physiol., 200, 67, 10.1152/ajplegacy.1961.200.1.67

Green, 1992, Metabolic adaptations to training precede changes in muscle mitochondrial capacity, J. Appl. Physiol., 72, 484, 10.1152/jappl.1992.72.2.484

Hallal, 2012, Global physical activity levels: surveillance progress, pitfalls, and prospects, Lancet, 380, 247, 10.1016/S0140-6736(12)60646-1

Handschin, 2007, Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals, J. Biol. Chem., 282, 30014, 10.1074/jbc.M704817200

Hargreaves, 2006, Skeletal muscle carbohydrate metabolism during exercise, 29

Haskell, 2007, Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association, Med. Sci. Sports Exerc., 39, 1423, 10.1249/mss.0b013e3180616b27

Henriksson, 1977, Time course of changes in human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity, Acta Physiol. Scand., 99, 91, 10.1111/j.1748-1716.1977.tb10356.x

Hirschey, 2010, SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation, Nature, 464, 121, 10.1038/nature08778

Holloszy, 1967, Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle, J. Biol. Chem., 242, 2278, 10.1016/S0021-9258(18)96046-1

Holloszy, 1984, Adaptations of skeletal muscle to endurance exercise and their metabolic consequences, J. Appl. Physiol., 56, 831, 10.1152/jappl.1984.56.4.831

Hood, 2001, Invited Review: contractile activity-induced mitochondrial biogenesis in skeletal muscle, J. Appl. Physiol., 90, 1137, 10.1152/jappl.2001.90.3.1137

Hornberger, 2006, The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle, Proc. Natl. Acad. Sci. USA, 103, 4741, 10.1073/pnas.0600678103

Horowitz, 2006, Adipose tissue lipid mobilization during exercise, 89

Horton, 1998, Fuel metabolism in men and women during and after long-duration exercise, J. Appl. Physiol., 85, 1823, 10.1152/jappl.1998.85.5.1823

Howald, 1985, Influences of endurance training on the ultrastructural composition of the different muscle fiber types in humans, Pflugers Arch., 403, 369, 10.1007/BF00589248

Howlett, 1998, Regulation of skeletal muscle glycogen phosphorylase and PDH at varying exercise power outputs, Am. J. Physiol., 275, R418

Hubal, 2005, Variability in muscle size and strength gain after unilateral resistance training, Med. Sci. Sports Exerc., 37, 964

Jäger, 2007, AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha, Proc. Natl. Acad. Sci. USA, 104, 12017, 10.1073/pnas.0705070104

Jentjens, 2003, Determinants of post-exercise glycogen synthesis during short-term recovery, Sports Med., 33, 117, 10.2165/00007256-200333020-00004

Jiang, 1996, Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1, J. Biol. Chem., 271, 17771, 10.1074/jbc.271.30.17771

Jing, 2011, Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production, Proc. Natl. Acad. Sci. USA, 108, 14608, 10.1073/pnas.1111308108

Kahn, 2005, AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism, Cell Metab., 1, 15, 10.1016/j.cmet.2004.12.003

Keller, 2011, A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype, J. Appl. Physiol., 110, 46, 10.1152/japplphysiol.00634.2010

Kiens, 2006, Skeletal muscle lipid metabolism in exercise and insulin resistance, Physiol. Rev., 86, 205, 10.1152/physrev.00023.2004

Kiens, 1998, Utilization of skeletal muscle triacylglycerol during postexercise recovery in humans, Am. J. Physiol., 275, E332

Kjaer, 2006, Hepatic metabolism during exercise, 45

Klossner, 2009, Mechano-transduction to muscle protein synthesis is modulated by FAK, Eur. J. Appl. Physiol., 106, 389, 10.1007/s00421-009-1032-7

Knab, 2010, Does the difference between physically active and couch potato lie in the dopamine system?, Int. J. Biol. Sci., 6, 133, 10.7150/ijbs.6.133

Knowler, 2002, Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin, N. Engl. J. Med., 346, 393, 10.1056/NEJMoa012512

Koopman, 2005, A single session of resistance exercise enhances insulin sensitivity for at least 24 h in healthy men, Eur. J. Appl. Physiol., 94, 180, 10.1007/s00421-004-1307-y

Koopman, 2006, Intramyocellular lipid and glycogen content are reduced following resistance exercise in untrained healthy males, Eur. J. Appl. Physiol., 96, 525, 10.1007/s00421-005-0118-0

Kumar, 2009, Age-related differences in the dose-response relationship of muscle protein synthesis to resistance exercise in young and old men, J. Physiol., 587, 211, 10.1113/jphysiol.2008.164483

Lagouge, 2006, Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha, Cell, 127, 1109, 10.1016/j.cell.2006.11.013

Lanza, 2008, Endurance exercise as a countermeasure for aging, Diabetes, 57, 2933, 10.2337/db08-0349

Leblanc, 2004, Effects of 7 wk of endurance training on human skeletal muscle metabolism during submaximal exercise, J. Appl. Physiol., 97, 2148, 10.1152/japplphysiol.00517.2004

Lee, 1995, Wortmannin inhibits insulin-stimulated but not contraction-stimulated glucose transport activity in skeletal muscle, FEBS Lett., 361, 51, 10.1016/0014-5793(95)00147-2

Leick, 2008, PGC-1alpha is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle, Am. J. Physiol. Endocrinol. Metab., 294, E463, 10.1152/ajpendo.00666.2007

Lin, 2005, Metabolic control through the PGC-1 family of transcription coactivators, Cell Metab., 1, 361, 10.1016/j.cmet.2005.05.004

Little, 2010, A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms, J. Physiol., 588, 1011, 10.1113/jphysiol.2009.181743

Little, 2011, An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1α and activates mitochondrial biogenesis in human skeletal muscle, Am. J. Physiol. Regul. Integr. Comp. Physiol., 300, R1303, 10.1152/ajpregu.00538.2010

Liu, 2005, Activity-dependent and -independent nuclear fluxes of HDAC4 mediated by different kinases in adult skeletal muscle, J. Cell Biol., 168, 887, 10.1083/jcb.200408128

Long, 2004, Exercise-induced mitogen-activated protein kinase signalling in skeletal muscle, Proc. Nutr. Soc., 63, 227, 10.1079/PNS2004346

Louis, 2007, Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle, J. Appl. Physiol., 103, 1744, 10.1152/japplphysiol.00679.2007

Lowell, 2005, Mitochondrial dysfunction and type 2 diabetes, Science, 307, 384, 10.1126/science.1104343

Macaluso, 2004, Muscle strength, power and adaptations to resistance training in older people, Eur. J. Appl. Physiol., 91, 450, 10.1007/s00421-003-0991-3

Mahoney, 2005, Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise, FASEB J., 19, 1498, 10.1096/fj.04-3149fje

Mason, 2004, Loss of skeletal muscle HIF-1alpha results in altered exercise endurance, PLoS Biol., 2, e288, 10.1371/journal.pbio.0020288

Maxwell, 1999, The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis, Nature, 399, 271, 10.1038/20459

McCarthy, 2007, MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy, J. Appl. Physiol., 102, 306, 10.1152/japplphysiol.00932.2006

McCarthy, 2009, Evidence of MyomiR network regulation of beta-myosin heavy chain gene expression during skeletal muscle atrophy, Physiol. Genomics, 39, 219, 10.1152/physiolgenomics.00042.2009

McCarthy, 2011, Effective fiber hypertrophy in satellite cell-depleted skeletal muscle, Development, 138, 3657, 10.1242/dev.068858

McGee, 2004, Exercise and myocyte enhancer factor 2 regulation in human skeletal muscle, Diabetes, 53, 1208, 10.2337/diabetes.53.5.1208

McGee, 2008, AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5, Diabetes, 57, 860, 10.2337/db07-0843

McGee, 2009, Exercise-induced histone modifications in human skeletal muscle, J. Physiol., 587, 5951, 10.1113/jphysiol.2009.181065

Merrill, 1997, AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle, Am. J. Physiol., 273, E1107

Mikines, 1988, Effect of physical exercise on sensitivity and responsiveness to insulin in humans, Am. J. Physiol., 254, E248

Moritani, 1979, Neural factors versus hypertrophy in the time course of muscle strength gain, Am. J. Phys. Med., 58, 115

Nader, 2001, Intracellular signaling specificity in skeletal muscle in response to different modes of exercise, J. Appl. Physiol., 90, 1936, 10.1152/jappl.2001.90.5.1936

Narkar, 2008, AMPK and PPARdelta agonists are exercise mimetics, Cell, 134, 405, 10.1016/j.cell.2008.06.051

Nemoto, 2005, SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1alpha, J. Biol. Chem., 280, 16456, 10.1074/jbc.M501485200

Nielsen, 2010, Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle, J. Physiol., 588, 4029, 10.1113/jphysiol.2010.189860

O’Connor, 2007, Last word on point:counterpoint: satellite cell addition is/is not obligatory for skeletal muscle hypertrophy, J. Appl. Physiol., 103, 1107, 10.1152/japplphysiol.00502.2007

O’Gorman, 2006, Exercise training increases insulin-stimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes, Diabetologia, 49, 2983, 10.1007/s00125-006-0457-3

O’Neil, 2009, The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions, J. Physiol., 587, 3691, 10.1113/jphysiol.2009.173609

Pedersen, 2012, Muscles, exercise and obesity: skeletal muscle as a secretory organ, Nat. Rev. Endocrinol., 8, 457, 10.1038/nrendo.2012.49

Perry, 2010, Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle, J. Physiol., 588, 4795, 10.1113/jphysiol.2010.199448

Perseghin, 1996, Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects, N. Engl. J. Med., 335, 1357, 10.1056/NEJM199610313351804

Petersen, 2012, Infusion with the antioxidant N-acetylcysteine attenuates early adaptive responses to exercise in human skeletal muscle, Acta Physiol. (Oxf.), 204, 382, 10.1111/j.1748-1716.2011.02344.x

Petrella, 2006, Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women, Am. J. Physiol. Endocrinol. Metab., 291, E937, 10.1152/ajpendo.00190.2006

Petrella, 2008, Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis, J. Appl. Physiol., 104, 1736, 10.1152/japplphysiol.01215.2007

Phillips, 1996, Progressive effect of endurance training on metabolic adaptations in working skeletal muscle, Am. J. Physiol., 270, E265

Phillips, 1997, Mixed muscle protein synthesis and breakdown after resistance exercise in humans, Am. J. Physiol., 273, E99

Philp, 2011, Signals mediating skeletal muscle remodeling by resistance exercise: PI3-kinase independent activation of mTORC1, J. Appl. Physiol., 110, 561, 10.1152/japplphysiol.00941.2010

Pilegaard, 2003, Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle, J. Physiol., 546, 851, 10.1113/jphysiol.2002.034850

Podolsky, 1983, Force generation and shortening in skeletal muscle, 173

Pogozelski, 2009, p38gamma mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice, PLoS ONE, 4, e7934, 10.1371/journal.pone.0007934

Powers, 1994, Influence of exercise and fiber type on antioxidant enzyme activity in rat skeletal muscle, Am. J. Physiol., 266, R375

Powers, 2010, Reactive oxygen species are signalling molecules for skeletal muscle adaptation, Exp. Physiol., 95, 1, 10.1113/expphysiol.2009.050526

Puigserver, 2001, Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1, Mol. Cell, 8, 971, 10.1016/S1097-2765(01)00390-2

Raney, 2008, Evidence for the involvement of CaMKII and AMPK in Ca2+-dependent signaling pathways regulating FA uptake and oxidation in contracting rodent muscle, J. Appl. Physiol., 104, 1366, 10.1152/japplphysiol.01282.2007

Raue, 2012, Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults, J. Appl. Physiol., 112, 1625, 10.1152/japplphysiol.00435.2011

Rennie, 2004, Control of the size of the human muscle mass, Annu. Rev. Physiol., 66, 799, 10.1146/annurev.physiol.66.052102.134444

Richardson, 1995, Myoglobin O2 desaturation during exercise. Evidence of limited O2 transport, J. Clin. Invest., 96, 1916, 10.1172/JCI118237

Romijn, 1993, Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration, Am. J. Physiol., 265, E380

Rose, 2006, Ca2+-calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise, J. Physiol., 574, 889, 10.1113/jphysiol.2006.111757

Safdar, 2011, Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice, Proc. Natl. Acad. Sci. USA, 108, 4135, 10.1073/pnas.1019581108

Safdar, 2011, Exercise increases mitochondrial PGC-1alpha content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis, J. Biol. Chem., 286, 10605, 10.1074/jbc.M110.211466

Sahlin, 1987, Redox state and lactate accumulation in human skeletal muscle during dynamic exercise, Biochem. J., 245, 551, 10.1042/bj2450551

Sale, 1987, Influence of exercise and training on motor unit activation, Exerc. Sport Sci. Rev., 15, 95, 10.1249/00003677-198700150-00008

Sale, 1988, Neural adaptation to resistance training, Med. Sci. Sports Exerc., 20, S135, 10.1249/00005768-198810001-00009

Saltin, 1983, Skeletal muscle adaptability: significance for metabolism and performance, 555

Sandri, 2008, Signaling in muscle atrophy and hypertrophy, Physiology (Bethesda), 23, 160

Sandri, 2004, Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy, Cell, 117, 399, 10.1016/S0092-8674(04)00400-3

Schenk, 2007, Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance, J. Clin. Invest., 117, 1690, 10.1172/JCI30566

Schiaffino, 2011, Fiber types in mammalian skeletal muscles, Physiol. Rev., 91, 1447, 10.1152/physrev.00031.2010

Schmutz, 2006, Endurance training modulates the muscular transcriptome response to acute exercise, Pflugers Arch., 451, 678, 10.1007/s00424-005-1497-0

Schwer, 2008, Conserved metabolic regulatory functions of sirtuins, Cell Metab., 7, 104, 10.1016/j.cmet.2007.11.006

Sigal, 2007, Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial, Ann. Intern. Med., 147, 357, 10.7326/0003-4819-147-6-200709180-00005

Spina, 1996, Mitochondrial enzymes increase in muscle in response to 7–10 days of cycle exercise, J. Appl. Physiol., 80, 2250, 10.1152/jappl.1996.80.6.2250

Spriet, 2003, Regulatory mechanisms in the interaction between carbohydrate and lipid oxidation during exercise, Acta Physiol. Scand., 178, 443, 10.1046/j.1365-201X.2003.01152.x

Stellingwerff, 2007, Significant intramyocellular lipid use during prolonged cycling in endurance-trained males as assessed by three different methodologies, Am. J. Physiol. Endocrinol. Metab., 292, E1715, 10.1152/ajpendo.00678.2006

Talanian, 2010, Exercise training increases sarcolemmal and mitochondrial fatty acid transport proteins in human skeletal muscle, Am. J. Physiol. Endocrinol. Metab., 299, E180, 10.1152/ajpendo.00073.2010

Taylor, 2008, Mitochondria and cellular oxygen sensing in the HIF pathway, Biochem. J., 409, 19, 10.1042/BJ20071249

Terzis, 2008, Resistance exercise-induced increase in muscle mass correlates with p70S6 kinase phosphorylation in human subjects, Eur. J. Appl. Physiol., 102, 145, 10.1007/s00421-007-0564-y

Timmons, 2010, Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans, J. Appl. Physiol., 108, 1487, 10.1152/japplphysiol.01295.2009

Tremblay, 1994, Impact of exercise intensity on body fatness and skeletal muscle metabolism, Metabolism, 43, 814, 10.1016/0026-0495(94)90259-3

van Loon, 2001, The effects of increasing exercise intensity on muscle fuel utilisation in humans, J. Physiol., 536, 295, 10.1111/j.1469-7793.2001.00295.x

van Loon, 2003, Intramyocellular lipids form an important substrate source during moderate intensity exercise in endurance-trained males in a fasted state, J. Physiol., 553, 611, 10.1113/jphysiol.2003.052431

van Rooij, 2009, A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance, Dev. Cell, 17, 662, 10.1016/j.devcel.2009.10.013

Vogt, 2001, Molecular adaptations in human skeletal muscle to endurance training under simulated hypoxic conditions, J. Appl. Physiol., 91, 173, 10.1152/jappl.2001.91.1.173

Vollaard, 2009, Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance, J. Appl. Physiol., 106, 1479, 10.1152/japplphysiol.91453.2008

Wagenmakers, 1991, Carbohydrate supplementation, glycogen depletion, and amino acid metabolism during exercise, Am. J. Physiol., 260, E883

Wang, 2012, Myostatin inhibition induces muscle fibre hypertrophy prior to satellite cell activation, J. Physiol., 590, 2151, 10.1113/jphysiol.2011.226001

Wang, 2004, Regulation of muscle fiber type and running endurance by PPARdelta, PLoS Biol., 2, e294, 10.1371/journal.pbio.0020294

Watt, 2010, Triacylglycerol lipases and metabolic control: implications for health and disease, Am. J. Physiol. Endocrinol. Metab., 299, E162, 10.1152/ajpendo.00698.2009

Wende, 2007, A role for the transcriptional coactivator PGC-1alpha in muscle refueling, J. Biol. Chem., 282, 36642, 10.1074/jbc.M707006200

Whitham, 2012, Contraction-induced interleukin-6 gene transcription in skeletal muscle is regulated by c-Jun terminal kinase/activator protein-1, J. Biol. Chem., 287, 10771, 10.1074/jbc.M111.310581

Widrick, 2002, Functional properties of human muscle fibers after short-term resistance exercise training, Am. J. Physiol. Regul. Integr. Comp. Physiol., 283, R408, 10.1152/ajpregu.00120.2002

Wilkinson, 2008, Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle, J. Physiol., 586, 3701, 10.1113/jphysiol.2008.153916

Winder, 1996, Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise, Am. J. Physiol., 270, E299

Wojtaszewski, 2000, Isoform-specific and exercise intensity-dependent activation of 5′-AMP-activated protein kinase in human skeletal muscle, J. Physiol., 528, 221, 10.1111/j.1469-7793.2000.t01-1-00221.x

Wolfe, 1990, Role of triglyceride-fatty acid cycle in controlling fat metabolism in humans during and after exercise, Am. J. Physiol., 258, E382

Wong, 1990, Protein metabolism in rat gastrocnemius muscle after stimulated chronic concentric exercise, J. Appl. Physiol., 69, 1709, 10.1152/jappl.1990.69.5.1709

Wretman, 2001, Effects of concentric and eccentric contractions on phosphorylation of MAPK(erk1/2) and MAPK(p38) in isolated rat skeletal muscle, J. Physiol., 535, 155, 10.1111/j.1469-7793.2001.00155.x

Wright, 2004, Ca2+ and AMPK both mediate stimulation of glucose transport by muscle contractions, Diabetes, 53, 330, 10.2337/diabetes.53.2.330

Wright, 2007, Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression, J. Biol. Chem., 282, 194, 10.1074/jbc.M606116200

Wu, 1999, Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1, Cell, 98, 115, 10.1016/S0092-8674(00)80611-X

Wu, 2002, Regulation of mitochondrial biogenesis in skeletal muscle by CaMK, Science, 296, 349, 10.1126/science.1071163

Yu, 2001, Marathon running increases ERK1/2 and p38 MAP kinase signalling to downstream targets in human skeletal muscle, J. Physiol., 536, 273, 10.1111/j.1469-7793.2001.00273.x

Yu, 2003, Metabolic and mitogenic signal transduction in human skeletal muscle after intense cycling exercise, J. Physiol., 546, 327, 10.1113/jphysiol.2002.034223

Zurlo, 1990, Skeletal muscle metabolism is a major determinant of resting energy expenditure, J. Clin. Invest., 86, 1423, 10.1172/JCI114857