1932

Abstract

Homeostatic systems mount adaptive responses to meet the energy demands of the cell and to compensate for dysfunction in cellular compartments. Such surveillance systems are also active at the organismal level: Nutrient and stress sensing in one tissue can lead to changes in other tissues. Here, we review the emerging understanding of the role of skeletal muscle in regulating physiological homeostasis and disease progression in other tissues. Muscle-specific genetic interventions can induce systemic effects indirectly, via changes in the mass and metabolic demand of muscle, and directly, via the release of muscle-derived cytokines (myokines) and metabolites (myometabolites) in response to nutrients and stress. In turn, myokines and myometabolites signal to various target tissues in an autocrine, paracrine, and endocrine manner, thereby determining organismal resilience to aging, disease, and environmental challenges. We propose that tailoring muscle systemic signaling by modulating myokine and myometabolite levels may combat many degenerative diseases and delay aging.

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2016-02-10
2024-05-08
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Literature Cited

  1. Veatch JR, McMurray MA, Nelson ZW, Gottschling DE. 1.  2009. Mitochondrial dysfunction leads to nuclear genome instability via an iron-sulfur cluster defect. Cell 137:1247–58 [Google Scholar]
  2. Taylor RC, Berendzen KM, Dillin A. 2.  2014. Systemic stress signalling: understanding the cell non-autonomous control of proteostasis. Nat. Rev. Mol. Cell Biol. 15:211–17 [Google Scholar]
  3. Metter EJ, Talbot LA, Schrager M, Conwit R. 3.  2002. Skeletal muscle strength as a predictor of all-cause mortality in healthy men. J. Gerontol. A 57:B359–65 [Google Scholar]
  4. Nair KS. 4.  2005. Aging muscle. Am. J. Clin. Nutr. 81:953–63 [Google Scholar]
  5. Ruiz JR, Sui X, Lobelo F, Morrow JR Jr, Jackson AW. 5.  et al. 2008. Association between muscular strength and mortality in men: prospective cohort study. BMJ 337a439
  6. Demontis F, Piccirillo R, Goldberg AL, Perrimon N. 6.  2013. The influence of skeletal muscle on systemic aging and lifespan. Aging Cell 12:943–49 [Google Scholar]
  7. Demontis F, Piccirillo R, Goldberg AL, Perrimon N. 7.  2013. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models. Dis. Model. Mech. 6:1339–52 [Google Scholar]
  8. Piccirillo R, Demontis F, Perrimon N, Goldberg AL. 8.  2014. Mechanisms of muscle growth and atrophy in mammals and Drosophila. Dev. Dyn. 243:201–15 [Google Scholar]
  9. Kim JK, Michael MD, Previs SF, Peroni OD, Mauvais-Jarvis F. 9.  et al. 2000. Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle. J. Clin. Investig. 105:1791–97 [Google Scholar]
  10. Brüning JC, Michael MD, Winnay JN, Hayashi T, Hörsch D. 10.  et al. 1998. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol. Cell 2:559–69 [Google Scholar]
  11. Burns JM, Johnson DK, Watts A, Swerdlow RH, Brooks WM. 11.  2010. Reduced lean mass in early Alzheimer disease and its association with brain atrophy. Arch. Neurol. 67:428–33 [Google Scholar]
  12. Kuo YM, Kokjohn TA, Watson MD, Woods AS, Cotter RJ. 12.  et al. 2000. Elevated Aβ42 in skeletal muscle of Alzheimer disease patients suggests peripheral alterations of AβPP metabolism. Am. J. Pathol. 156:797–805 [Google Scholar]
  13. Demontis F, Perrimon N. 13.  2009. Integration of Insulin receptor/Foxo signaling and dMyc activity during muscle growth regulates body size in Drosophila. Development 136:983–93 [Google Scholar]
  14. Ghosh A, Rideout EJ, Grewal SS. 14.  2014. TIF-IA-dependent regulation of ribosome synthesis in Drosophila muscle is required to maintain systemic insulin signaling and larval growth. PLOS Genet. 10:e1004750 [Google Scholar]
  15. Knapp JR, Davie JK, Myer A, Meadows E, Olson EN, Klein WH. 15.  2006. Loss of myogenin in postnatal life leads to normal skeletal muscle but reduced body size. Development 133:601–10 [Google Scholar]
  16. Anderson CM, Hu J, Barnes RM, Heidt AB, Cornelissen I, Black BL. 16.  2015. Myocyte enhancer factor 2C function in skeletal muscle is required for normal growth and glucose metabolism in mice. Skelet. Muscle 5:7 [Google Scholar]
  17. Wang YX, Zhang CL, Yu RT, Cho HK, Nelson MC. 17.  et al. 2004. Regulation of muscle fiber type and running endurance by PPARδ. PLOS Biol. 2:e294 [Google Scholar]
  18. Luquet S, Lopez-Soriano J, Holst D, Fredenrich A, Melki J. 18.  et al. 2003. Peroxisome proliferator–activated receptor delta controls muscle development and oxidative capability. FASEB J. 17:2299–301 [Google Scholar]
  19. Izumiya Y, Hopkins T, Morris C, Sato K, Zeng L. 19.  et al. 2008. Fast/glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice. Cell Metab. 7:159–72 [Google Scholar]
  20. McPherron AC, Lee SJ. 20.  2002. Suppression of body fat accumulation in myostatin-deficient mice. J. Clin. Investig. 109:595–601 [Google Scholar]
  21. McPherron AC, Lawler AM, Lee SJ. 21.  1997. Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member. Nature 387:83–90 [Google Scholar]
  22. Ryder JW, Bassel-Duby R, Olson EN, Zierath JR. 22.  2003. Skeletal muscle reprogramming by activation of calcineurin improves insulin action on metabolic pathways. J. Biol. Chem. 278:44298–304 [Google Scholar]
  23. Zhou X, Wang JL, Lu J, Song Y, Kwak KS. 23.  et al. 2010. Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell 142:531–43 [Google Scholar]
  24. Pedersen BK, Febbraio MA. 24.  2012. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat. Rev. Endocrinol. 8:457–65 [Google Scholar]
  25. Webb AE, Brunet A. 25.  2014. FOXO transcription factors: key regulators of cellular quality control. Trends Biochem. Sci. 39:159–69 [Google Scholar]
  26. Demontis F, Perrimon N. 26.  2010. FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell 143:813–25 [Google Scholar]
  27. Bai H, Kang P, Hernandez AM, Tatar M. 27.  2013. Activin signaling targeted by insulin/dFOXO regulates aging and muscle proteostasis in Drosophila. PLOS Genet. 9:e1003941 [Google Scholar]
  28. Tsai S, Sitzmann JM, Dastidar SG, Rodriguez AA, Vu SL. 28.  et al. 2015. Muscle-specific 4E-BP1 signaling activation improves metabolic parameters during aging and obesity. J. Clin. Investig. 125:2952–64 [Google Scholar]
  29. Morley JF, Morimoto RI. 29.  2004. Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol. Biol. Cell 15:657–64 [Google Scholar]
  30. van Oosten–Hawle P, Porter RS, Morimoto RI. 30.  2013. Regulation of organismal proteostasis by transcellular chaperone signaling. Cell 153:1366–78 [Google Scholar]
  31. Sugi T, Nishida Y, Mori I. 31.  2011. Regulation of behavioral plasticity by systemic temperature signaling in Caenorhabditis elegans. Nat. Neurosci. 14:984–92 [Google Scholar]
  32. Scott BA, Avidan MS, Crowder CM. 32.  2002. Regulation of hypoxic death in C. elegans by the insulin/IGF receptor homolog DAF-2. Science 296:2388–91 [Google Scholar]
  33. Tohyama D, Yamaguchi A. 33.  2010. A critical role of SNF1A/dAMPKα (Drosophila AMP-activated protein kinase α) in muscle on longevity and stress resistance in Drosophila melanogaster. Biochem. Biophys. Res. Commun 394:112–18 [Google Scholar]
  34. Vrailas-Mortimer A, del Rivero T, Mukherjee S, Nag S, Gaitanidis A. 34.  et al. 2011. A muscle-specific p38 MAPK/Mef2/MnSOD pathway regulates stress, motor function, and life span in Drosophila. Dev. Cell 21:783–95 [Google Scholar]
  35. Patel PH, Tamanoi F. 35.  2006. Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress. J. Cell Sci. 119:4285–92 [Google Scholar]
  36. Chamoli M, Singh A, Malik Y, Mukhopadhyay A. 36.  2014. A novel kinase regulates dietary restriction–mediated longevity in Caenorhabditis elegans. Aging Cell 13:641–55 [Google Scholar]
  37. Katewa SD, Demontis F, Kolipinski M, Hubbard A, Gill MS. 37.  et al. 2012. Intramyocellular fatty-acid metabolism plays a critical role in mediating responses to dietary restriction in Drosophila melanogaster. Cell Metab. 16:97–103 [Google Scholar]
  38. Hakimi P, Yang J, Casadesus G, Massillon D, Tolentino-Silva F. 38.  et al. 2007. Overexpression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse. J. Biol. Chem. 282:32844–55 [Google Scholar]
  39. Hanson RW, Hakimi P. 39.  2008. Born to run; the story of the PEPCK-Cmus mouse. Biochimie 90:838–42 [Google Scholar]
  40. Stenesen D, Suh JM, Seo J, Yu K, Lee KS. 40.  et al. 2013. Adenosine nucleotide biosynthesis and AMPK regulate adult life span and mediate the longevity benefit of caloric restriction in flies. Cell Metab. 17:101–12 [Google Scholar]
  41. Handschin C, Chin S, Li P, Liu F, Maratos-Flier E. 41.  et al. 2007. Skeletal muscle fiber–type switching, exercise intolerance, and myopathy in PGC-1α muscle-specific knock-out animals. J. Biol. Chem. 282:30014–21 [Google Scholar]
  42. Sczelecki S, Besse-Patin A, Abboud A, Kleiner S, Laznik-Bogoslavski D. 42.  et al. 2014. Loss of Pgc-1α expression in aging mouse muscle potentiates glucose intolerance and systemic inflammation. Am. J. Physiol. Endocrinol. Metab. 306:E157–67 [Google Scholar]
  43. Wenz T, Rossi SG, Rotundo RL, Spiegelman BM, Moraes CT. 43.  2009. Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging. PNAS 106:20405–10 [Google Scholar]
  44. Jager S, Handschin C, St.-Pierre J, Spiegelman BM. 44.  2007. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. PNAS 104:12017–22 [Google Scholar]
  45. Puigserver P, Rhee J, Lin J, Wu Z, Yoon JC. 45.  et al. 2001. Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARγ coactivator-1. Mol. Cell 8:971–82 [Google Scholar]
  46. Li B, Nolte LA, Ju JS, Han DH, Coleman T. 46.  et al. 2000. Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice. Nat. Med. 6:1115–20 [Google Scholar]
  47. Keipert S, Ost M, Chadt A, Voigt A, Ayala V. 47.  et al. 2013. Skeletal muscle uncoupling-induced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system. Am. J. Physiol. Endocrinol. Metab. 304:E495–506 [Google Scholar]
  48. Gates AC, Bernal-Mizrachi C, Chinault SL, Feng C, Schneider JG. 48.  et al. 2007. Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease. Cell Metab. 6:497–505 [Google Scholar]
  49. Keipert S, Voigt A, Klaus S. 49.  2011. Dietary effects on body composition, glucose metabolism, and longevity are modulated by skeletal muscle mitochondrial uncoupling in mice. Aging Cell 10:122–36 [Google Scholar]
  50. Duteil D, Chambon C, Ali F, Malivindi R, Zoll J. 50.  et al. 2010. The transcriptional coregulators TIF2 and SRC-1 regulate energy homeostasis by modulating mitochondrial respiration in skeletal muscles. Cell Metab. 12:496–508 [Google Scholar]
  51. Pospisilik JA, Knauf C, Joza N, Benit P, Orthofer M. 51.  et al. 2007. Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes. Cell 131:476–91 [Google Scholar]
  52. Owusu-Ansah E, Song W, Perrimon N. 52.  2013. Muscle mitohormesis promotes longevity via systemic repression of insulin signaling. Cell 155:699–712 [Google Scholar]
  53. Demontis F, Patel VK, Swindell WR, Perrimon N. 53.  2014. Intertissue control of the nucleolus via a myokine-dependent longevity pathway. Cell Rep. 7:1481–94 [Google Scholar]
  54. Patel VK, Demontis F. 54.  2014. GDF11/myostatin and aging. Aging 6:351–52 [Google Scholar]
  55. Doroudgar S, Glembotski CC. 55.  2011. The cardiokine story unfolds: ischemic stress–induced protein secretion in the heart. Trends Mol. Med. 17:207–14 [Google Scholar]
  56. Lee HY, Gattu AK, Camporez JP, Kanda S, Guigni B. 56.  et al. 2014. Muscle-specific activation of Ca2+/calmodulin-dependent protein kinase IV increases whole-body insulin action in mice. Diabetologia 57:1232–41 [Google Scholar]
  57. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L. 57.  et al. 2012. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481:463–68 [Google Scholar]
  58. Pekkala S, Wiklund PK, Hulmi JJ, Ahtiainen JP, Horttanainen M. 58.  et al. 2013. Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health?. J. Physiol. 591:5393–400 [Google Scholar]
  59. Timmons JA, Baar K, Davidsen PK, Atherton PJ. 59.  2012. Is irisin a human exercise gene?. Nature 488:E9–10, discussion E1 [Google Scholar]
  60. Raschke S, Elsen M, Gassenhuber H, Sommerfeld M, Schwahn U. 60.  et al. 2013. Evidence against a beneficial effect of irisin in humans. PLOS ONE 8:e73680 [Google Scholar]
  61. Servick K. 61.  2015. Biomedicine. Woes for ‘exercise hormone’. Science 347:1299 [Google Scholar]
  62. Albrecht E, Norheim F, Thiede B, Holen T, Ohashi T. 62.  et al. 2015. Irisin—a myth rather than an exercise-inducible myokine. Sci. Rep. 5:8889 [Google Scholar]
  63. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J. 63.  et al. 2014. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 19:302–9 [Google Scholar]
  64. Barra NG, Chew MV, Holloway AC, Ashkar AA. 64.  2012. Interleukin-15 treatment improves glucose homeostasis and insulin sensitivity in obese mice. Diabetes Obes. Metab. 14:190–93 [Google Scholar]
  65. Quinn LS, Anderson BG, Conner JD, Wolden-Hanson T. 65.  2013. IL-15 overexpression promotes endurance, oxidative energy metabolism, and muscle PPARδ, SIRT1, PGC-1α, and PGC-1β expression in male mice. Endocrinology 154:232–45 [Google Scholar]
  66. Quinn LS, Anderson BG, Strait-Bodey L, Stroud AM, Argiles JM. 66.  2009. Oversecretion of interleukin-15 from skeletal muscle reduces adiposity. Am. J. Physiol. Endocrinol. Metab. 296:E191–202 [Google Scholar]
  67. Ruas JL, White JP, Rao RR, Kleiner S, Brannan KT. 67.  et al. 2012. A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 151:1319–31 [Google Scholar]
  68. Rao RR, Long JZ, White JP, Svensson KJ, Lou J. 68.  et al. 2014. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell 157:1279–91 [Google Scholar]
  69. Yeh SH, Lai HL, Hsiao CY, Lin LW, Chuang YK. 69.  et al. 2014. Moderate physical activity of music aerobic exercise increases lymphocyte counts, specific subsets, and differentiation. J. Phys. Act. Health 11:1386–92 [Google Scholar]
  70. Pedersen L, Olsen CH, Pedersen BK, Hojman P. 70.  2012. Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle. Am. J. Physiol. Endocrinol. Metab. 302:E831–40 [Google Scholar]
  71. Staiger H, Haas C, Machann J, Werner R, Weisser M. 71.  et al. 2009. Muscle-derived angiopoietin-like protein 4 is induced by fatty acids via peroxisome proliferator–activated receptor (PPAR)-δ and is of metabolic relevance in humans. Diabetes 58:579–89 [Google Scholar]
  72. Feldman BJ, Streeper RS, Farese RV Jr, Yamamoto KR. 72.  2006. Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic effects. PNAS 103:15675–80 [Google Scholar]
  73. Ellingsgaard H, Hauselmann I, Schuler B, Habib AM, Baggio LL. 73.  et al. 2011. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat. Med. 17:1481–89 [Google Scholar]
  74. Ostrowski K, Rohde T, Zacho M, Asp S, Pedersen BK. 74.  1998. Evidence that interleukin-6 is produced in human skeletal muscle during prolonged running. J. Physiol. 508:3949–53 [Google Scholar]
  75. Kristiansen OP, Mandrup-Poulsen T. 75.  2005. Interleukin-6 and diabetes: the good, the bad, or the indifferent?. Diabetes 54:Suppl. 2114–24 [Google Scholar]
  76. Besse-Patin A, Montastier E, Vinel C, Castan-Laurell I, Louche K. 76.  et al. 2014. Effect of endurance training on skeletal muscle myokine expression in obese men: identification of apelin as a novel myokine. Int. J. Obes. 38:707–13 [Google Scholar]
  77. Miyatake S, Manabe Y, Inagaki A, Furuichi Y, Takagi M. 77.  et al. 2014. Macrophage migration inhibitory factor diminishes muscle glucose transport induced by insulin and AICAR in a muscle type–dependent manner. Biochem. Biophys. Res. Commun. 444:496–501 [Google Scholar]
  78. Galaup A, Gomez E, Souktani R, Durand M, Cazes A. 78.  et al. 2012. Protection against myocardial infarction and no-reflow through preservation of vascular integrity by angiopoietin-like 4. Circulation 125:140–49 [Google Scholar]
  79. Kersten S, Lichtenstein L, Steenbergen E, Mudde K, Hendriks HF. 79.  et al. 2009. Caloric restriction and exercise increase plasma ANGPTL4 levels in humans via elevated free fatty acids. Arterioscler. Thromb. Vasc. Biol. 29:969–74 [Google Scholar]
  80. Miyabe M, Ohashi K, Shibata R, Uemura Y, Ogura Y. 80.  et al. 2014. Muscle-derived follistatin-like 1 functions to reduce neointimal formation after vascular injury. Cardiovasc. Res. 103:111–20 [Google Scholar]
  81. Arany Z, Foo SY, Ma Y, Ruas JL, Bommi-Reddy A. 81.  et al. 2008. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α. Nature 451:1008–12 [Google Scholar]
  82. Aoi W, Naito Y, Takagi T, Tanimura Y, Takanami Y. 82.  et al. 2013. A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise. Gut 62:882–89 [Google Scholar]
  83. Hojman P, Dethlefsen C, Brandt C, Hansen J, Pedersen L, Pedersen BK. 83.  2011. Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth. Am. J. Physiol. Endocrinol. Metab. 301:E504–10 [Google Scholar]
  84. Aswad H, Forterre A, Wiklander OP, Vial G, Danty-Berger E. 84.  et al. 2014. Exosomes participate in the alteration of muscle homeostasis during lipid-induced insulin resistance in mice. Diabetologia 57:2155–64 [Google Scholar]
  85. Yoon JH, Kim D, Jang JH, Ghim J, Park S. 85.  et al. 2015. Proteomic analysis of the palmitate-induced myotube secretome reveals involvement of the annexin A1–FPR2 pathway in insulin resistance. Mol. Cell. Proteomics 14:882–92 [Google Scholar]
  86. White PJ, St.-Pierre P, Charbonneau A, Mitchell PL, St.-Amand E. 86.  et al. 2014. Protectin DX alleviates insulin resistance by activating a myokine-liver glucoregulatory axis. Nat. Med. 20:664–69 [Google Scholar]
  87. Chen T, Li Z, Zhang Y, Feng F, Wang X. 87.  et al. 2015. Muscle-selective knockout of AMPKα2 does not exacerbate diet-induced obesity probably related to altered myokines expression. Biochem. Biophys. Res. Commun. 458:449–55 [Google Scholar]
  88. Nishizawa H, Matsuda M, Yamada Y, Kawai K, Suzuki E. 88.  et al. 2004. Musclin, a novel skeletal muscle–derived secretory factor. J. Biol. Chem. 279:19391–95 [Google Scholar]
  89. Li YX, Cheng KC, Asakawa A, Kato I, Sato Y. 89.  et al. 2013. Role of musclin in the pathogenesis of hypertension in rat. PLOS ONE 8:e72004 [Google Scholar]
  90. Banzet S, Koulmann N, Sanchez H, Serrurier B, Peinnequin A, Bigard AX. 90.  2007. Musclin gene expression is strongly related to fast-glycolytic phenotype. Biochem. Biophys. Res. Commun. 353:713–18 [Google Scholar]
  91. Yasui A, Nishizawa H, Okuno Y, Morita K, Kobayashi H. 91.  et al. 2007. Foxo1 represses expression of musclin, a skeletal muscle–derived secretory factor. Biochem. Biophys. Res. Commun. 364:358–65 [Google Scholar]
  92. Seldin MM, Peterson JM, Byerly MS, Wei Z, Wong GW. 92.  2012. Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J. Biol. Chem. 287:11968–80 [Google Scholar]
  93. Seldin MM, Lei X, Tan SY, Stanson KP, Wei Z, Wong GW. 93.  2013. Skeletal muscle–derived myonectin activates the mammalian target of rapamycin (mTOR) pathway to suppress autophagy in liver. J. Biol. Chem. 288:36073–82 [Google Scholar]
  94. Kim KH, Jeong YT, Kim SH, Jung HS, Park KS. 94.  et al. 2013. Metformin-induced inhibition of the mitochondrial respiratory chain increases FGF21 expression via ATF4 activation. Biochem. Biophys. Res. Commun. 440:76–81 [Google Scholar]
  95. Keipert S, Ost M, Johann K, Imber F, Jastroch M. 95.  et al. 2014. Skeletal muscle mitochondrial uncoupling drives endocrine cross-talk through the induction of FGF21 as a myokine. Am. J. Physiol. Endocrinol. Metab. 306:E469–82 [Google Scholar]
  96. Tyynismaa H, Carroll CJ, Raimundo N, Ahola-Erkkila S, Wenz T. 96.  et al. 2010. Mitochondrial myopathy induces a starvation-like response. Hum. Mol. Genet. 19:3948–58 [Google Scholar]
  97. Izumiya Y, Bina HA, Ouchi N, Akasaki Y, Kharitonenkov A, Walsh K. 97.  2008. FGF21 is an Akt-regulated myokine. FEBS Lett. 582:3805–10 [Google Scholar]
  98. Hojman P, Pedersen M, Nielsen AR, Krogh-Madsen R, Yfanti C. 98.  et al. 2009. Fibroblast growth factor-21 is induced in human skeletal muscles by hyperinsulinemia. Diabetes 58:2797–801 [Google Scholar]
  99. Suomalainen A, Elo JM, Pietilainen KH, Hakonen AH, Sevastianova K. 99.  et al. 2011. FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study. Lancet Neurol. 10:806–18 [Google Scholar]
  100. Hede MS, Salimova E, Piszczek A, Perlas E, Winn N. 100.  et al. 2012. E-peptides control bioavailability of IGF-1. PLOS ONE 7:e51152 [Google Scholar]
  101. Zeng L, Akasaki Y, Sato K, Ouchi N, Izumiya Y, Walsh K. 101.  2010. Insulin-like 6 is induced by muscle injury and functions as a regenerative factor. J. Biol. Chem. 285:36060–69 [Google Scholar]
  102. Zeng L, Maruyama S, Nakamura K, Parker-Duffen JL, Adham IM. 102.  et al. 2014. The injury-induced myokine insulin-like 6 is protective in experimental autoimmune myositis. Skelet. Muscle 4:16 [Google Scholar]
  103. Negishi S, Li Y, Usas A, Fu FH, Huard J. 103.  2005. The effect of relaxin treatment on skeletal muscle injuries. Am. J. Sports Med. 33:1816–24 [Google Scholar]
  104. Mu X, Urso ML, Murray K, Fu F, Li Y. 104.  2010. Relaxin regulates MMP expression and promotes satellite cell mobilization during muscle healing in both young and aged mice. Am. J. Pathol. 177:2399–410 [Google Scholar]
  105. Serrano AL, Baeza-Raja B, Perdiguero E, Jardi M, Munoz-Canoves P. 105.  2008. Interleukin-6 is an essential regulator of satellite cell–mediated skeletal muscle hypertrophy. Cell Metab. 7:33–44 [Google Scholar]
  106. Broholm C, Laye MJ, Brandt C, Vadalasetty R, Pilegaard H. 106.  et al. 2011. LIF is a contraction-induced myokine stimulating human myocyte proliferation. J. Appl. Physiol. 111:251–59 [Google Scholar]
  107. Hunt LC, Tudor EM, White JD. 107.  2010. Leukemia inhibitory factor–dependent increase in myoblast cell number is associated with phosphotidylinositol 3-kinase–mediated inhibition of apoptosis and not mitosis. Exp. Cell Res. 316:1002–9 [Google Scholar]
  108. Guerci A, Lahoute C, Hebrard S, Collard L, Graindorge D. 108.  et al. 2012. Srf-dependent paracrine signals produced by myofibers control satellite cell–mediated skeletal muscle hypertrophy. Cell Metab. 15:25–37 [Google Scholar]
  109. Lafreniere JF, Mills P, Bouchentouf M, Tremblay JP. 109.  2006. Interleukin-4 improves the migration of human myogenic precursor cells in vitro and in vivo. Exp. Cell Res. 312:1127–41 [Google Scholar]
  110. Haugen F, Norheim F, Lian H, Wensaas AJ, Dueland S. 110.  et al. 2010. IL-7 is expressed and secreted by human skeletal muscle cells. Am. J. Physiol. Cell Physiol. 298:C807–16 [Google Scholar]
  111. Umemoto T, Furutani Y, Murakami M, Matsui T, Funaba M. 111.  2011. Endogenous Bmp4 in myoblasts is required for myotube formation in C2C12 cells. Biochim. Biophys. Acta 1810:1127–35 [Google Scholar]
  112. Horsley V, Pavlath GK. 112.  2003. Prostaglandin F stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway. J. Cell Biol. 161:111–18 [Google Scholar]
  113. Kanzleiter T, Rath M, Gorgens SW, Jensen J, Tangen DS. 113.  et al. 2014. The myokine decorin is regulated by contraction and involved in muscle hypertrophy. Biochem. Biophys. Res. Commun. 450:1089–94 [Google Scholar]
  114. Kishioka Y, Thomas M, Wakamatsu J, Hattori A, Sharma M. 114.  et al. 2008. Decorin enhances the proliferation and differentiation of myogenic cells through suppressing myostatin activity. J. Cell. Physiol. 215:856–67 [Google Scholar]
  115. Straino S, Germani A, Di Carlo A, Porcelli D, De Mori R. 115.  et al. 2004. Enhanced arteriogenesis and wound repair in dystrophin-deficient mdx mice. Circulation 110:3341–48 [Google Scholar]
  116. D'Amore PA, Brown RH Jr, Ku PT, Hoffman EP, Watanabe H. 116.  et al. 1994. Elevated basic fibroblast growth factor in the serum of patients with Duchenne muscular dystrophy. Ann. Neurol. 35:362–65 [Google Scholar]
  117. Voss MW, Vivar C, Kramer AF, van Praag H. 117.  2013. Bridging animal and human models of exercise-induced brain plasticity. Trends Cogn. Sci. 17:525–44 [Google Scholar]
  118. Klein AB, Williamson R, Santini MA, Clemmensen C, Ettrup A. 118.  et al. 2011. Blood BDNF concentrations reflect brain-tissue BDNF levels across species. Int. J. Neuropsychopharmacol. 14:347–53 [Google Scholar]
  119. Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH, Christie BR. 119.  2004. Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 124:71–79 [Google Scholar]
  120. Banks WA, Kastin AJ, Gutierrez EG. 120.  1994. Penetration of interleukin-6 across the murine blood-brain barrier. Neurosci. Lett. 179:53–56 [Google Scholar]
  121. Piya MK, Harte AL, Sivakumar K, Tripathi G, Voyias PD. 121.  et al. 2014. The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes. Am. J. Physiol. Endocrinol. Metab. 306:E512–18 [Google Scholar]
  122. Sarruf DA, Thaler JP, Morton GJ, German J, Fischer JD. 122.  et al. 2010. Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats. Diabetes 59:1817–24 [Google Scholar]
  123. Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS. 123.  et al. 2014. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 344:630–34 [Google Scholar]
  124. Raichlen DA, Polk JD. 124.  2013. Linking brains and brawn: exercise and the evolution of human neurobiology. Proc. R. Soc. B 280:20122250 [Google Scholar]
  125. Szlama G, Trexler M, Buday L, Patthy L. 125.  2015. K153R polymorphism in myostatin gene increases the rate of promyostatin activation by furin. FEBS Lett. 589:295–301 [Google Scholar]
  126. Garatachea N, Pinos T, Camara Y, Rodriguez-Romo G, Emanuele E. 126.  et al. 2013. Association of the K153R polymorphism in the myostatin gene and extreme longevity. Age 35:2445–54 [Google Scholar]
  127. Sinha M, Jang YC, Oh J, Khong D, Wu EY. 127.  et al. 2014. Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science 344:649–52 [Google Scholar]
  128. Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS. 128.  et al. 2014. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 344:630–34 [Google Scholar]
  129. Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI. 129.  et al. 2014. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat. Med. 20:659–63 [Google Scholar]
  130. Loffredo FS, Steinhauser ML, Jay SM, Gannon J, Pancoast JR. 130.  et al. 2013. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell 153:828–39 [Google Scholar]
  131. Zhang Y, Shao J, Wang Z, Yang T, Liu S. 131.  et al. 2015. Growth differentiation factor 11 is a protective factor for osteoblastogenesis by targeting PPARγ. Gene 557:209–14 [Google Scholar]
  132. Egerman MA, Cadena SM, Gilbert JA, Meyer A, Nelson HN. 132.  et al. 2015. GDF11 increases with age and inhibits skeletal muscle regeneration. Cell Metab. 22:164–74 [Google Scholar]
  133. Houtkooper RH, Argmann C, Houten SM, Canto C, Jeninga EH. 133.  et al. 2011. The metabolic footprint of aging in mice. Sci. Rep. 1:134 [Google Scholar]
  134. Wolfe RR. 134.  2006. The underappreciated role of muscle in health and disease. Am. J. Clin. Nutr. 84:475–82 [Google Scholar]
  135. Rennie MJ, Tipton KD. 135.  2000. Protein and amino acid metabolism during and after exercise and the effects of nutrition. Annu. Rev. Nutr. 20:457–83 [Google Scholar]
  136. Nair KS, Short KR. 136.  2005. Hormonal and signaling role of branched-chain amino acids. J. Nutr. 135:S1547–52 [Google Scholar]
  137. Jousse C, Averous J, Bruhat A, Carraro V, Mordier S, Fafournoux P. 137.  2004. Amino acids as regulators of gene expression: molecular mechanisms. Biochem. Biophys. Res. Commun. 313:447–52 [Google Scholar]
  138. Brooks GA. 138.  2009. Cell-cell and intracellular lactate shuttles. J. Physiol. 587:5591–600 [Google Scholar]
  139. Philp A, Macdonald AL, Watt PW. 139.  2005. Lactate—a signal coordinating cell and systemic function. J. Exp. Biol. 208:4561–75 [Google Scholar]
  140. Corkey BE, Shirihai O. 140.  2012. Metabolic master regulators: sharing information among multiple systems. Trends Endocrinol. Metab. 23:594–601 [Google Scholar]
  141. Brosnan ME, Letto J. 141.  1991. Interorgan metabolism of valine. Amino Acids 1:29–35 [Google Scholar]
  142. Trabold O, Wagner S, Wicke C, Scheuenstuhl H, Hussain MZ. 142.  et al. 2003. Lactate and oxygen constitute a fundamental regulatory mechanism in wound healing. Wound Repair. Regen. 11:504–9 [Google Scholar]
  143. Hashimoto T, Hussien R, Oommen S, Gohil K, Brooks GA. 143.  2007. Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis. FASEB J. 21:2602–12 [Google Scholar]
  144. Bergersen LH. 144.  2015. Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain interaction. J. Cereb. Blood Flow Metab. 35:176–85 [Google Scholar]
  145. van Hall G, van der Vusse GJ, Soderlund K, Wagenmakers AJ. 145.  1995. Deamination of amino acids as a source for ammonia production in human skeletal muscle during prolonged exercise. J. Physiol. 489:1251–61 [Google Scholar]
  146. Graham TE, MacLean DA. 146.  1992. Ammonia and amino acid metabolism in human skeletal muscle during exercise. Can. J. Physiol. Pharmacol. 70:132–41 [Google Scholar]
  147. Calvani R, Joseph AM, Adhihetty PJ, Miccheli A, Bossola M. 147.  et al. 2012. Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy. Biol. Chem. 394:393–414 [Google Scholar]
  148. He C, Sumpter R Jr, Levine B. 148.  2012. Exercise induces autophagy in peripheral tissues and in the brain. Autophagy 8:1548–51 [Google Scholar]
  149. Eng CH, Yu K, Lucas J, White E, Abraham RT. 149.  2010. Ammonia derived from glutaminolysis is a diffusible regulator of autophagy. Sci. Signal. 3ra31
  150. Hellsten Y. 150.  1999. The effect of muscle contraction on the regulation of adenosine formation in rat skeletal muscle cells. J. Physiol. 518:3761–68 [Google Scholar]
  151. Vergauwen L, Hespel P, Richter EA. 151.  1994. Adenosine receptors mediate synergistic stimulation of glucose uptake and transport by insulin and by contractions in rat skeletal muscle. J. Clin. Investig. 93:974–81 [Google Scholar]
  152. Zuberova M, Fenckova M, Simek P, Janeckova L, Dolezal T. 152.  2010. Increased extracellular adenosine in Drosophila that are deficient in adenosine deaminase activates a release of energy stores leading to wasting and death. Dis. Models Mech. 3:773–84 [Google Scholar]
  153. Han DH, Hansen PA, Nolte LA, Holloszy JO. 153.  1998. Removal of adenosine decreases the responsiveness of muscle glucose transport to insulin and contractions. Diabetes 47:1671–75 [Google Scholar]
  154. Gnad T, Scheibler S, von Kugelgen I, Scheele C, Kilic A. 154.  et al. 2014. Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors. Nature 516:395–99 [Google Scholar]
  155. Sandona D, Danieli-Betto D, Germinario E, Biral D, Martinello T. 155.  et al. 2005. The T-tubule membrane ATP-operated P2X4 receptor influences contractility of skeletal muscle. FASEB J. 19:1184–86 [Google Scholar]
  156. Araya R, Riquelme MA, Brandan E, Saez JC. 156.  2004. The formation of skeletal muscle myotubes requires functional membrane receptors activated by extracellular ATP. Brain Res. Brain Res. Rev. 47:174–88 [Google Scholar]
  157. Kim MS, Lee J, Ha J, Kim SS, Kong Y. 157.  et al. 2002. ATP stimulates glucose transport through activation of P2 purinergic receptors in C2C12 skeletal muscle cells. Arch. Biochem. Biophys. 401:205–14 [Google Scholar]
  158. Burnstock G. 158.  2006. Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol. Rev. 58:58–86 [Google Scholar]
  159. Michel T, Feron O. 159.  1997. Nitric oxide synthases: which, where, how, and why?. J. Clin. Investig. 100:2146–52 [Google Scholar]
  160. Nguyen HX, Tidball JG. 160.  2003. Expression of a muscle-specific, nitric oxide synthase transgene prevents muscle membrane injury and reduces muscle inflammation during modified muscle use in mice. J. Physiol. 550:347–56 [Google Scholar]
  161. Hamann M, Chamoin MC, Portalier P, Bernheim L, Baroffio A. 161.  et al. 1995. Synthesis and release of an acetylcholine-like compound by human myoblasts and myotubes. J. Physiol. 489:3791–803 [Google Scholar]
  162. Roberts LD, Bostrom P, O'Sullivan JF, Schinzel RT, Lewis GD. 162.  et al. 2014. β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors. Cell Metab. 19:96–108 [Google Scholar]
  163. Shimomura Y, Honda T, Shiraki M, Murakami T, Sato J. 163.  et al. 2006. Branched-chain amino acid catabolism in exercise and liver disease. J. Nutr. 136:S250–53 [Google Scholar]
  164. Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L. 164.  et al. 2003. The Orphan G protein–coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 278:11312–19 [Google Scholar]
  165. Patti GJ, Tautenhahn R, Johannsen D, Kalisiak E, Ravussin E. 165.  et al. 2014. Meta-analysis of global metabolomic data identifies metabolites associated with life-span extension. Metabolomics 10:737–43 [Google Scholar]
  166. Agudelo LZ, Femenia T, Orhan F, Porsmyr-Palmertz M, Goiny M. 166.  et al. 2014. Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. Cell 159:33–45 [Google Scholar]
  167. Waldrop TG, Stremel RW. 167.  1989. Muscular contraction stimulates posterior hypothalamic neurons. Am. J. Physiol. Regul. Integr. Comp. Physiol. 256:R348–56 [Google Scholar]
  168. Coll AP, Yeo GS. 168.  2013. The hypothalamus and metabolism: integrating signals to control energy and glucose homeostasis. Curr. Opin. Pharmacol. 13:970–76 [Google Scholar]
  169. Sagot Y, Rosse T, Vejsada R, Perrelet D, Kato AC. 169.  1998. Differential effects of neurotrophic factors on motoneuron retrograde labeling in a murine model of motoneuron disease. J. Neurosci. 18:1132–41 [Google Scholar]
  170. Koliatsos VE, Clatterbuck RE, Winslow JW, Cayouette MH, Price DL. 170.  1993. Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 10:359–67 [Google Scholar]
  171. Gomez-Pinilla F, Ying Z, Opazo P, Roy RR, Edgerton VR. 171.  2001. Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle. Eur. J. Neurosci. 13:1078–84 [Google Scholar]
  172. Bongiovanni A, Romancino DP, Campos Y, Paterniti G, Qiu X. 172.  et al. 2012. Alix protein is substrate of Ozz-E3 ligase and modulates actin remodeling in skeletal muscle. J. Biol. Chem. 287:12159–71 [Google Scholar]
  173. Ritzenthaler S, Suzuki E, Chiba A. 173.  2000. Postsynaptic filopodia in muscle cells interact with innervating motoneuron axons. Nat. Neurosci. 3:1012–17 [Google Scholar]
  174. Demontis F, Dahmann C. 174.  2007. Apical and lateral cell protrusions interconnect epithelial cells in live Drosophila wing imaginal discs. Dev. Dyn. 236:3408–18 [Google Scholar]
  175. Kornberg TB, Roy S. 175.  2014. Cytonemes as specialized signaling filopodia. Development 141:729–36 [Google Scholar]
  176. Norheim F, Raastad T, Thiede B, Rustan AC, Drevon CA, Haugen F. 176.  2011. Proteomic identification of secreted proteins from human skeletal muscle cells and expression in response to strength training. Am. J. Physiol. Endocrinol. Metab. 301:E1013–21 [Google Scholar]
  177. Hopkins BD, Fine B, Steinbach N, Dendy M, Rapp Z. 177.  et al. 2013. A secreted PTEN phosphatase that enters cells to alter signaling and survival. Science 341:399–402 [Google Scholar]
  178. Kwiatkowski DJ, Mehl R, Izumo S, Nadal-Ginard B, Yin HL. 178.  1988. Muscle is the major source of plasma gelsolin. J. Biol. Chem. 263:8239–43 [Google Scholar]
  179. Swynghedauw B. 179.  1986. Developmental and functional adaptation of contractile proteins in cardiac and skeletal muscles. Physiol. Rev. 66:710–71 [Google Scholar]
  180. Manabe Y, Takagi M, Nakamura-Yamada M, Goto-Inoue N, Taoka M. 180.  et al. 2014. Redox proteins are constitutively secreted by skeletal muscle. J. Physiol. Sci. 64:401–9 [Google Scholar]
  181. Jang A, Lee HJ, Suk JE, Jung JW, Kim KP, Lee SJ. 181.  2010. Non-classical exocytosis of α-synuclein is sensitive to folding states and promoted under stress conditions. J. Neurochem. 113:1263–74 [Google Scholar]
  182. Choo HJ, Kim BW, Kwon OB, Lee CS, Choi JS, Ko YG. 182.  2008. Secretion of adenylate kinase 1 is required for extracellular ATP synthesis in C2C12 myotubes. Exp. Mol. Med. 40:220–28 [Google Scholar]
  183. Vult von Steyern F, Josefsson JO. 183.  1995. Secretion of plasminogen activator and lysosomal enzymes from mouse skeletal muscle: effect of denervation. J. Cell. Physiol. 164:555–61 [Google Scholar]
  184. Romancino DP, Paterniti G, Campos Y, De Luca A, Di Felice V. 184.  et al. 2013. Identification and characterization of the nano-sized vesicles released by muscle cells. FEBS Lett. 587:1379–84 [Google Scholar]
  185. Guescini M, Guidolin D, Vallorani L, Casadei L, Gioacchini AM. 185.  et al. 2010. C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction. Exp. Cell Res. 316:1977–84 [Google Scholar]
  186. Forterre A, Jalabert A, Chikh K, Pesenti S, Euthine V. 186.  et al. 2014. Myotube-derived exosomal miRNAs downregulate Sirtuin1 in myoblasts during muscle cell differentiation. Cell Cycle 13:78–89 [Google Scholar]
  187. Panakova D, Sprong H, Marois E, Thiele C, Eaton S. 187.  2005. Lipoprotein particles are required for Hedgehog and Wingless signalling. Nature 435:58–65 [Google Scholar]
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