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Myokines are a group of cytokines that exert a major influence on muscle metabolism through autocrine mechanisms and are involved in para- or endocrine regulation in organs outside of muscle tissue, such as the pancreas, adipose tissue, liver, heart, bone, gastrointestinal tract, and brain. In the future, these findings could be crucial for the identification of important biomarkers used for the monitoring of physical activity in the treatment of pathologies such as intensive care-associated muscle wasting, sarcopenia, diabetes, neurodegenerative diseases, etc. As skeletal muscle tissue is intrinsically linked to multiple types of tissues and organs metabolically, functionally, and most importantly, regionally, there can be a significant overlap between the auto- and paracrine effects of myokines, depending on the presence of that myokine. The following section will discuss the auto-, para-, and endocrine effects of some of the myo-inducible cytokines on skeletal muscles and adjacent tissue types.<\/jats:p>","DOI":"10.33549\/physiolres.935751","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T13:23:19Z","timestamp":1768310599000},"page":"S37","source":"Crossref","is-referenced-by-count":14,"title":["Skeletal Muscle as an Auto-, Para- and Endocrine Organ: The Role of Myokines in Muscle Metabolism and Other Metabolic Organs"],"prefix":"10.33549","author":[{"given":"L","family":"Horv\u00e1th","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Peka\u0159","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"\u0160vagera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Hork\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Mr\u00e1z","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Bu\u017ega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"19169","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"1.\tFrontera WR, Ochala J. Skeletal Muscle: A Brief Review of Structure and Function. Calcif Tissue Int 2015;96:183-195. https:\/\/doi.org\/10.1007\/s00223-014-9915-y","DOI":"10.1007\/s00223-014-9915-y"},{"key":"ref1","doi-asserted-by":"crossref","unstructured":"2.\tGoldstein MS. Humoral Nature of the Hypoglycemic Factor of Muscular Work. Diabetes 1961;10:232-234. https:\/\/doi.org\/10.2337\/diab.10.3.232","DOI":"10.2337\/diab.10.3.232"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"3.\tCannon JG, Kluger MJ. Endogenous Pyrogen Activity in Human Plasma After Exercise. Science 1983;220:617-619. https:\/\/doi.org\/10.1126\/science.6836306","DOI":"10.1126\/science.6836306"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"4.\tOstrowski K, Hermann C, Bangash A, Schjerling P, Nielsen JN, Pedersen BK. A trauma-like elevation of plasma cytokines in humans in response to treadmill running. J Physiol 1998;513(Pt 3):889-894. https:\/\/doi.org\/10.1111\/j.1469-7793.1998.889ba.x","DOI":"10.1111\/j.1469-7793.1998.889ba.x"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"5.\tPedersen BK, Steensberg A, Fischer C, Keller C, Keller P, Plomgaard P, Febbraio M, Saltin B. Searching for the exercise factor: is IL-6 a candidate? J Muscle Res Cell Motil 2003;24:113-119. https:\/\/doi.org\/10.1023\/A:1026070911202","DOI":"10.1023\/A:1026070911202"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"6.\tChow LS, Gerszten RE, Taylor JM, Pedersen BK, Van Praag H, Trappe S, Febbraio MA, et al. Exerkines in health, resilience and disease. Nat Rev Endocrinol 2022;18:273-289. https:\/\/doi.org\/10.1038\/s41574-022-00641-2","DOI":"10.1038\/s41574-022-00641-2"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"7.\tIizuka K, Machida T, Hirafuji M. Skeletal Muscle Is an Endocrine Organ. J Pharmacol Sci 2014;125:125-131. https:\/\/doi.org\/10.1254\/jphs.14R02CP","DOI":"10.1254\/jphs.14R02CP"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"8.\tScisciola L, Fontanella RA, Surina, Cataldo V, Paolisso G, Barbieri M. Sarcopenia and Cognitive Function: Role of Myokines in Muscle Brain Cross-Talk. Life 2021;11:173. https:\/\/doi.org\/10.3390\/life11020173","DOI":"10.3390\/life11020173"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"9.\tBalakrishnan R, Thurmond DC. Mechanisms by Which Skeletal Muscle Myokines Ameliorate Insulin Resistance. Int J Mol Sci 2022;23:4636. https:\/\/doi.org\/10.3390\/ijms23094636","DOI":"10.3390\/ijms23094636"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"10.\tFlorin A, Lambert C, Sanchez C, Zappia J, Durieux N, Tieppo AM, Mobasheri A, Henrotin Y. The secretome of skeletal muscle cells: A systematic review. Osteoarthr Cartil Open 2020;2:100019. https:\/\/doi.org\/10.1016\/j.ocarto.2019.100019","DOI":"10.1016\/j.ocarto.2019.100019"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"11.\tLeg\u00e5rd GE, Pedersen BK. Muscle as an Endocrine Organ. In: Muscle and Exercise Physiology. ZOLADZ JE (ed.), Elsevier, 2019, pp 285-307. https:\/\/doi.org\/10.1016\/B978-0-12-814593-7.00013-X","DOI":"10.1016\/B978-0-12-814593-7.00013-X"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"12.\tBrooks GA, Osmond AD, Arevalo JA, Curl CC, Duong JJ, Horning MA, Moreno Santillan DD, Leija RG. Lactate as a major myokine and exerkine. Nat Rev Endocrinol 2022;18:712-712. https:\/\/doi.org\/10.1038\/s41574-022-00724-0","DOI":"10.1038\/s41574-022-00724-0"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"13.\tGuescini M, Guidolin D, Vallorani L, Casadei L, Gioacchini AM, Tibollo P, Battistelli M, et al. C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction. Exp Cell Res 2010;316:1977-1984. https:\/\/doi.org\/10.1016\/j.yexcr.2010.04.006","DOI":"10.1016\/j.yexcr.2010.04.006"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"14.\tLe Bihan M-C, Bigot A, Jensen SS, Dennis JL, Rogowska-Wrzesinska A, Lain\u00e9 J, Gache V, et al. In-depth analysis of the secretome identifies three major independent secretory pathways in differentiating human myoblasts. J Proteomics 2012;77:344-356. https:\/\/doi.org\/10.1016\/j.jprot.2012.09.008","DOI":"10.1016\/j.jprot.2012.09.008"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"15.\tReeh H, Rudolph N, Billing U, Christen H, Streif S, Bullinger E, Schliemann-Bullinger M, et al. Response to IL-6 trans- and IL-6 classic signalling is determined by the ratio of the IL-6 receptor \u03b1 to gp130 expression: fusing experimental insights and dynamic modelling. Cell Commun Signal 2019;17:46. https:\/\/doi.org\/10.1186\/s12964-019-0356-0","DOI":"10.1186\/s12964-019-0356-0"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"16.\tWeitz HT, Ettich J, Rafii P, Wittich C, Schultz L, Frank NC, Heise D, et al. Interleukin\u201011 receptor is an alternative \u03b1\u2010receptor for interleukin\u20106 and the chimeric cytokine IC7. FEBS J 2025;292:523-536. https:\/\/doi.org\/10.1111\/febs.17309","DOI":"10.1111\/febs.17309"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"17.\tKeller C, Steensberg A, Hansen AK, Fischer CP, Plomgaard P, Pedersen BK. Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle. J Appl Physiol 2005;99:2075-2079. https:\/\/doi.org\/10.1152\/japplphysiol.00590.2005","DOI":"10.1152\/japplphysiol.00590.2005"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"18.\tSerrano AL, Baeza-Raja B, Perdiguero E, Jard\u00ed M, Mu\u00f1oz-C\u00e1noves P. Interleukin-6 Is an Essential Regulator of Satellite Cell-Mediated Skeletal Muscle Hypertrophy. Cell Metab 2008;7:33-44. https:\/\/doi.org\/10.1016\/j.cmet.2007.11.011","DOI":"10.1016\/j.cmet.2007.11.011"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"19.\tMu\u00f1oz\u2010C\u00e1noves P, Scheele C, Pedersen BK, Serrano AL. Interleukin\u20106 myokine signaling in skeletal muscle: a double\u2010edged sword? FEBS J 2013;280:4131-4148. https:\/\/doi.org\/10.1111\/febs.12338","DOI":"10.1111\/febs.12338"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"20.\tGoodman MN. Interleukin-6 Induces Skeletal Muscle Protein Breakdown in Rats. Exp Biol Med 1994;205:182-185. https:\/\/doi.org\/10.3181\/00379727-205-43695","DOI":"10.3181\/00379727-205-43695"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"21.\tHaddad F, Zaldivar F, Cooper DM, Adams GR. IL-6-induced skeletal muscle atrophy. J Appl Physiol 2005;98:911-917. https:\/\/doi.org\/10.1152\/japplphysiol.01026.2004","DOI":"10.1152\/japplphysiol.01026.2004"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"22.\tVan Hall G, Steensberg A, Fischer C, Keller C, M\u00f8ller K, Moseley P, Pedersen BK. Interleukin-6 Markedly Decreases Skeletal Muscle Protein Turnover and Increases Nonmuscle Amino Acid Utilization in Healthy Individuals. J Clin Endocrinol Metab 2008;93:2851-2858. https:\/\/doi.org\/10.1210\/jc.2007-2223","DOI":"10.1210\/jc.2007-2223"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"23.\tTrinh B, Peletier M, Simonsen C, Plomgaard P, Karstoft K, Klarlund Pedersen B, et al. Blocking endogenous IL-6 impairs mobilization of free fatty acids during rest and exercise in lean and obese men. Cell Rep Med 2021;2:100396. https:\/\/doi.org\/10.1016\/j.xcrm.2021.100396","DOI":"10.1016\/j.xcrm.2021.100396"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"24.\tWedell-Neergaard A-S, Lang Lehrskov L, Christensen RH, Legaard GE, Dorph E, Larsen MK, Launbo N, et al. Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial. Cell Metab 2019;29:844-855.e3. https:\/\/doi.org\/10.1016\/j.cmet.2018.12.007","DOI":"10.1016\/j.cmet.2018.12.007"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"25.\tCarey MT, Millar SR, Elliott PS, Navarro P, Harrington JM, Perry IJ, Phillips CM. Plant-based diet adherence is associated with metabolic health status in adults living with and without obesity. Eur J Nutr 2024;63:2235-2246. https:\/\/doi.org\/10.1007\/s00394-024-03399-7","DOI":"10.1007\/s00394-024-03399-7"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"26.\tLin W, Song H, Shen J, Wang J, Yang Y, Yang Y, Cao J, et al. Functional role of skeletal muscle-derived interleukin-6 and its effects on lipid metabolism. Front Physiol 2023;14:1110926. https:\/\/doi.org\/10.3389\/fphys.2023.1110926","DOI":"10.3389\/fphys.2023.1110926"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"27.\tDeng C, Chen H. Brain-derived neurotrophic factor\/tropomyosin receptor kinase B signaling in spinal muscular atrophy and amyotrophic lateral sclerosis. Neurobiol Dis 2024;190:106377. https:\/\/doi.org\/10.1016\/j.nbd.2023.106377","DOI":"10.1016\/j.nbd.2023.106377"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"28.\tMatthews VB, \u00c5str\u00f6m M-B, Chan MHS, Bruce CR, Krabbe KS, Prelovsek O, Akerstr\u00f6m T, et al. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia 2009;52:1409-1418. https:\/\/doi.org\/10.1007\/s00125-009-1364-1","DOI":"10.1007\/s00125-009-1364-1"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"29.\tVillamil-Parra W, Moscoso-Loaiza L. Effects of physical exercise on Irisin and BDNF concentrations, and their relationship with cardiometabolic and mental health of individuals with Metabolic Syndrome: A Systematic Review. Exp Gerontol 2024;198:112640. https:\/\/doi.org\/10.1016\/j.exger.2024.112640","DOI":"10.1016\/j.exger.2024.112640"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"30.\tLi Y, Li F, Qin D, Chen H, Wang J, Wang J, Song S, et al. The role of brain derived neurotrophic factor in central nervous system. Front Aging Neurosci 2022;14:986443. https:\/\/doi.org\/10.3389\/fnagi.2022.986443","DOI":"10.3389\/fnagi.2022.986443"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"31.\tZhang J, Xiong A, Yang Y, Cao Y, Yang M, Su C, Lei M, et al. In-Depth Proteomic Analysis of Tissue Interstitial Fluid Reveals Biomarker Candidates Related to Varying Differentiation Statuses in Gastric Adenocarcinoma. J Proteome Res 2025;24:1386-1401. https:\/\/doi.org\/10.1021\/acs.jproteome.4c01067","DOI":"10.1021\/acs.jproteome.4c01067"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"32.\tClow C, Jasmin BJ. Brain-derived Neurotrophic Factor Regulates Satellite Cell Differentiation and Skeltal Muscle Regeneration. Mol Biol Cell 2010;21:2182-2190. https:\/\/doi.org\/10.1091\/mbc.e10-02-0154","DOI":"10.1091\/mbc.e10-02-0154"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"33.\tAhuja P, Ng CF, Pang BPS, Chan WS, Tse MCL, Bi X, Kwan HR, et al. Muscle-generated BDNF (brain derived neurotrophic factor) maintains mitochondrial quality control in female mice. Autophagy 2022;18:1367-1384. https:\/\/doi.org\/10.1080\/15548627.2021.1985257","DOI":"10.1080\/15548627.2021.1985257"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"34.\tBrown AD, Marko AD, Marko DM, Baranowski BJ, Silvera S, Finch MS, Yang AJ, et al. Brain\u2010derived neurotrophic factor drives muscle adaptation similar to aerobic training in mice. FASEB J 2025;39:e70321. https:\/\/doi.org\/10.1096\/fj.202402421R","DOI":"10.1096\/fj.202402421R"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"35.\tXiong J, Liao J, Liu X, Zhang Z, Adams J, Pacifici R, Ye K. A TrkB agonist prodrug prevents bone loss via inhibiting asparagine endopeptidase and increasing osteoprotegerin. Nat Commun 2022;13:4820. https:\/\/doi.org\/10.1038\/s41467-022-32435-5","DOI":"10.1038\/s41467-022-32435-5"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"36.\tAk\u00e7a \u0130\u0130, Bodur A, Kahraman C, Abidin \u0130, Ayd\u0131n-Abidin S, Alver A. The regulation of adipokines related to obesity and diabetes is sensitive to BDNF levels and adipose tissue location. Hormones 2022;21:295-303. https:\/\/doi.org\/10.1007\/s42000-022-00364-z","DOI":"10.1007\/s42000-022-00364-z"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"37.\tMu A, Wales TE, Zhou H, Draga-Colet\u0103 S-V, Gorgulla C, Blackmore KA, Mittenb\u00fchler MJ, et al. Irisin acts through its integrin receptor in a two-step process involving extracellular Hsp90\u03b1. Mol Cell 2023;83:1903-1920.e12. https:\/\/doi.org\/10.1016\/j.molcel.2023.05.008","DOI":"10.1016\/j.molcel.2023.05.008"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"38.\tCai L, Tan M, Tan W, Zeng X, Wan N, Wong SH-S, O'Reilly J, et al. Associations of Circulating Irisin Concentrations With Cardiometabolic Risk Factors Among Children Vary by Physical Activity or Sedentary Time Levels. Front Endocrinol 2019;10:549. https:\/\/doi.org\/10.3389\/fendo.2019.00549","DOI":"10.3389\/fendo.2019.00549"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"39.\tReza MM, Subramaniyam N, Sim CM, Ge X, Sathiakumar D, McFarlane C, Sharma M, Kambadur R. Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and rescues denervation-induced atrophy. Nat Commun 2017;8:1104. https:\/\/doi.org\/10.1038\/s41467-017-01131-0","DOI":"10.1038\/s41467-017-01131-0"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"40.\tColaianni G, Cuscito C, Mongelli T, Pignataro P, Buccoliero C, Liu P, Lu P, et al. The myokine irisin increases cortical bone mass. Proc Natl Acad Sci U S A 2015;112:12157-12162. https:\/\/doi.org\/10.1073\/pnas.1516622112","DOI":"10.1073\/pnas.1516622112"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"41.\tFagundo AB, Jim\u00e9nez-Murcia S, Giner-Bartolom\u00e9 C, Ag\u00fcera Z, Sauchelli S, Pardo M, Crujeiras AB, et al. Modulation of Irisin and Physical Activity on Executive Functions in Obesity and Morbid obesity. Sci Rep 2016;6:30820. https:\/\/doi.org\/10.1038\/srep30820","DOI":"10.1038\/srep30820"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"42.\tDi Giacomo G, Vadal\u00e0 G, Ambrosio L, Cicione C, Tilotta V, Cannata F, Russo F, et al. Irisin inhibits tenocyte response to inflammation in vitro: New insights into tendon\u2010muscle cross\u2010talk. J Orthop Res 2023;41:2195-2204. https:\/\/doi.org\/10.1002\/jor.25586","DOI":"10.1002\/jor.25586"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"43.\tAsadi Y, Gorjipour F, Behrouzifar S, Vakili A. Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke. Neurochem Res 2018;43:1549-1560. https:\/\/doi.org\/10.1007\/s11064-018-2569-9","DOI":"10.1007\/s11064-018-2569-9"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"44.\tKalkan \u00d6F, Akta\u015f O, S\u00fcrmeneli YE, Alver A, \u00d6zcan M, \u015eahin Z. Does irisin has neuroprotective effect against diabetes induced neuropathy in male rats? Arch Physiol Biochem 2023;129:439-448. https:\/\/doi.org\/10.1080\/13813455.2020.1835985","DOI":"10.1080\/13813455.2020.1835985"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"45.\tKong X, Yao T, Zhou P, Kazak L, Tenen D, Lyubetskaya A, Dawes BA, et al. Brown Adipose Tissue Controls Skeletal Muscle Function via the Secretion of Myostatin. Cell Metab 2018;28:631-643.e3. https:\/\/doi.org\/10.1016\/j.cmet.2018.07.004","DOI":"10.1016\/j.cmet.2018.07.004"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"46.\tBreitbart A, Auger-Messier M, Molkentin JD, Heineke J. Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting. Am J Physiol Heart Circ Physiol 2011;300:H1973-H1982. https:\/\/doi.org\/10.1152\/ajpheart.00200.2011","DOI":"10.1152\/ajpheart.00200.2011"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"47.\tVerzola D, Barisione C, Picciotto D, Garibotto G, Koppe L. Emerging role of myostatin and its inhibition in the setting of chronic kidney disease. Kidney Int 2019;95:506-517. https:\/\/doi.org\/10.1016\/j.kint.2018.10.010","DOI":"10.1016\/j.kint.2018.10.010"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"48.\tDay JW, Howell K, Place A, Long K, Rossello J, Kertesz N, Nomikos G. Advances and limitations for the treatment of spinal muscular atrophy. BMC Pediatr 2022;22:632. https:\/\/doi.org\/10.1186\/s12887-022-03671-x","DOI":"10.1186\/s12887-022-03671-x"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"49.\tHan HQ, Zhou X, Mitch WE, Goldberg AL. Myostatin\/activin pathway antagonism: Molecular basis and therapeutic potential. Int J Biochem Cell Biol 2013;45:2333-2347. https:\/\/doi.org\/10.1016\/j.biocel.2013.05.019","DOI":"10.1016\/j.biocel.2013.05.019"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"50.\tMcCroskery S, Thomas M, Maxwell L, Sharma M, Kambadur R. Myostatin negatively regulates satellite cell activation and self-renewal. J Cell Biol 2003;162:1135-1147. https:\/\/doi.org\/10.1083\/jcb.200207056","DOI":"10.1083\/jcb.200207056"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"51.\tLokireddy S, Mouly V, Butler-Browne G, Gluckman PD, Sharma M, Kambadur R, McFarlane C. Myostatin promotes the wasting of human myoblast cultures through promoting ubiquitin-proteasome pathway-mediated loss of sarcomeric proteins. Am J Physiol Cell Physiol 2011;301:C1316-C1324. https:\/\/doi.org\/10.1152\/ajpcell.00114.2011","DOI":"10.1152\/ajpcell.00114.2011"},{"key":"ref51","doi-asserted-by":"crossref","unstructured":"52.\tMcPherron AC, Lee S-J. Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci U S A 1997;94:12457-12461. https:\/\/doi.org\/10.1073\/pnas.94.23.12457","DOI":"10.1073\/pnas.94.23.12457"},{"key":"ref52","doi-asserted-by":"crossref","unstructured":"53.\tAbati E, Manini A, Comi GP, Corti S. Inhibition of myostatin and related signaling pathways for the treatment of muscle atrophy in motor neuron diseases. Cell Mol Life Sci 2022;79:374. https:\/\/doi.org\/10.1007\/s00018-022-04408-w","DOI":"10.1007\/s00018-022-04408-w"},{"key":"ref53","doi-asserted-by":"crossref","unstructured":"54.\tShan T, Liang X, Bi P, Kuang S. Myostatin knockout drives browning of white adipose tissue through activating the AMPK\u2010PGC1\u03b1\u2010Fndc5 pathway in muscle. FASEB J 2013;27:1981-1989. https:\/\/doi.org\/10.1096\/fj.12-225755","DOI":"10.1096\/fj.12-225755"},{"key":"ref54","doi-asserted-by":"crossref","unstructured":"55.\tDong J, Dong Y, Dong Y, Chen F, Mitch WE, Zhang L. Inhibition of myostatin in mice improves insulin sensitivity via irisin-mediated cross talk between muscle and adipose tissues. Int J Obes 2016;40:434-442. https:\/\/doi.org\/10.1038\/ijo.2015.200","DOI":"10.1038\/ijo.2015.200"},{"key":"ref55","doi-asserted-by":"crossref","unstructured":"56.\tMastaitis J, Gomez D, Le Rouzic V, Stec M, Khan N, Na E, McWilliams T, et al. 207-OR: Myostatin Inhibition Synergizes with GLP-1R Agonism to Accelerate Weight Loss in Male, Obese Nonhuman Primates. Diabetes 2023;72(Suppl. 1):207-OR. https:\/\/doi.org\/10.2337\/db23-207-OR","DOI":"10.2337\/db23-207-OR"},{"key":"ref56","doi-asserted-by":"crossref","unstructured":"57.\tMendias CL, Bakhurin KI, Faulkner JA. Tendons of myostatin-deficient mice are small, brittle, and hypocellular. Proc Natl Acad Sci U S A 2008;105:388-393. https:\/\/doi.org\/10.1073\/pnas.0707069105","DOI":"10.1073\/pnas.0707069105"},{"key":"ref57","doi-asserted-by":"crossref","unstructured":"58.\tAmemiya H, Yamamoto M, Higa K, Watanabe G, Taniguchi S, Kitamura K, Jeong J, et al. Effects of Myostatin on Nuclear Morphology at the Myotendinous Junction. Int J Mol Sci 2023;24:6634. https:\/\/doi.org\/10.3390\/ijms24076634","DOI":"10.3390\/ijms24076634"},{"key":"ref58","doi-asserted-by":"crossref","unstructured":"59.\tEliasson P, Andersson T, Kulas J, Seemann P, Aspenberg P. Myostatin in tendon maintenance and repair. Growth Factors 2009;27:247-254. https:\/\/doi.org\/10.1080\/08977190903052539","DOI":"10.1080\/08977190903052539"},{"key":"ref59","doi-asserted-by":"crossref","unstructured":"60.\tHamrick MW, Shi X, Zhang W, Pennington C, Thakore H, Haque M, Kang B, et al. Loss of myostatin (GDF8) function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading. Bone 2007;40:1544-1553. https:\/\/doi.org\/10.1016\/j.bone.2007.02.012","DOI":"10.1016\/j.bone.2007.02.012"},{"key":"ref60","doi-asserted-by":"crossref","unstructured":"61.\tElkasrawy M, Immel D, Wen X, Liu X, Liang L-F, Hamrick MW. Immunolocalization of Myostatin (GDF-8) Following Musculoskeletal Injury and the Effects of Exogenous Myostatin on Muscle and Bone Healing. J Histochem Cytochem 2012;60:22-30. https:\/\/doi.org\/10.1369\/0022155411425389","DOI":"10.1369\/0022155411425389"},{"key":"ref61","doi-asserted-by":"crossref","unstructured":"62.\tDeng Z, Fan T, Xiao C, Tian H, Zheng Y, Li C, He J. TGF-\u03b2 signaling in health, disease and therapeutics. Signal Transduct Target Ther 2024;9:61. https:\/\/doi.org\/10.1038\/s41392-024-01764-w","DOI":"10.1038\/s41392-024-01764-w"},{"key":"ref62","doi-asserted-by":"crossref","unstructured":"63.\tYndestad A, Haukeland JW, Dahl TB, Halvorsen B, Aukrust P. Activin A in Nonalcoholic Fatty Liver Disease. In: Vitamins & Hormones. Litwack G (ed.), Elsevier, 2011, pp 323-342. https:\/\/doi.org\/10.1016\/B978-0-12-385961-7.00015-9","DOI":"10.1016\/B978-0-12-385961-7.00015-9"},{"key":"ref63","doi-asserted-by":"crossref","unstructured":"64.\tYaden BC, Wang YX, Wilson JM, Culver AE, Milner A, Datta-Mannan A, Shetler P, et al. Inhibition of Activin A Ameliorates Skeletal Muscle Injury and Rescues Contractile Properties by Inducing Efficient Remodeling in Female Mice. Am J Pathol 2014;184:1152-1166. https:\/\/doi.org\/10.1016\/j.ajpath.2013.12.029","DOI":"10.1016\/j.ajpath.2013.12.029"},{"key":"ref64","doi-asserted-by":"crossref","unstructured":"65.\tDing H, Zhang G, Sin KWT, Liu Z, Lin R-K, Li M, Li Y-P. Activin A induces skeletal muscle catabolism via p38\u03b2 mitogen\u2010activated protein kinase. J Cachexia Sarcopenia Muscle 2017;8:202-212. https:\/\/doi.org\/10.1002\/jcsm.12145","DOI":"10.1002\/jcsm.12145"},{"key":"ref65","doi-asserted-by":"crossref","unstructured":"66.\tLee S-J, Lee Y-S, Zimmers TA, Soleimani A, Matzuk MM, Tsuchida K, Cohn RD, Barton ER. Regulation of Muscle Mass by Follistatin and Activins. Mol Endocrinol 2010;24:1998-2008. https:\/\/doi.org\/10.1210\/me.2010-0127","DOI":"10.1210\/me.2010-0127"},{"key":"ref66","doi-asserted-by":"crossref","unstructured":"67.\tHansen J, Brandt C, Nielsen AR, Hojman P, Whitham M, Febbraio MA, Pedersen BK, Plomgaard P. Exercise Induces a Marked Increase in Plasma Follistatin: Evidence That Follistatin Is a Contraction-Induced Hepatokine. Endocrinology 2011;152:164-171. https:\/\/doi.org\/10.1210\/en.2010-0868","DOI":"10.1210\/en.2010-0868"},{"key":"ref67","doi-asserted-by":"crossref","unstructured":"68.\tLiu Y, Lehar A, Rydzik R, Chandok H, Lee Y-S, Youngstrom DW, George J, et al. Local versus systemic control of bone and skeletal muscle mass by components of the transforming growth factor-\u03b2 signaling pathway. Proc Natl Acad Sci U S A 2021;118:e2111401118. https:\/\/doi.org\/10.1073\/pnas.2111401118","DOI":"10.1073\/pnas.2111401118"},{"key":"ref68","doi-asserted-by":"crossref","unstructured":"69.\tWinbanks CE, Weeks KL, Thomson RE, Sepulveda PV, Beyer C, Qian H, Chen JL, et al. Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin. J Cell Biol 2012;197:997-1008. https:\/\/doi.org\/10.1083\/jcb.201109091","DOI":"10.1083\/jcb.201109091"},{"key":"ref69","doi-asserted-by":"crossref","unstructured":"70.\tGiesige CR, Wallace LM, Heller KN, Eidahl JO, Saad NY, Fowler AM, Pyne NK, et al. AAV-mediated follistatin gene therapy improves functional outcomes in the TIC-DUX4 mouse model of FSHD. JCI Insight 2018;3:e123538. https:\/\/doi.org\/10.1172\/jci.insight.123538","DOI":"10.1172\/jci.insight.123538"},{"key":"ref70","doi-asserted-by":"crossref","unstructured":"71.\tSubbotina E, Sierra A, Zhu Z, Gao Z, Koganti SRK, Reyes S, Stepniak E, et al. Musclin is an activity-stimulated myokine that enhances physical endurance. Proc Natl Acad Sci U S A 2015;112:16042-16047. https:\/\/doi.org\/10.1073\/pnas.1514250112","DOI":"10.1073\/pnas.1514250112"},{"key":"ref71","doi-asserted-by":"crossref","unstructured":"72.\tKang Y, Park S, Kim S, Koh H. Handgrip Strength Among Korean Adolescents With Metabolic Syndrome in 2014-2015. J Clin Densitom 2020;23:271-277. https:\/\/doi.org\/10.1016\/j.jocd.2018.09.002","DOI":"10.1016\/j.jocd.2018.09.002"},{"key":"ref72","doi-asserted-by":"crossref","unstructured":"73.\tChoi KM. Sarcopenia and Sarcopenic Obesity. Endocrinol Metab 2013;28:86-86. https:\/\/doi.org\/10.3803\/EnM.2013.28.2.86","DOI":"10.3803\/EnM.2013.28.2.86"},{"key":"ref73","doi-asserted-by":"crossref","unstructured":"74.\tJin L, Han S, Lv X, Li X, Zhang Z, Kuang H, Chen Z, et al. The muscle-enriched myokine Musclin impairs beige fat thermogenesis and systemic energy homeostasis via Tfr1\/PKA signaling in male mice. Nat Commun 2023;14:4257. https:\/\/doi.org\/10.1038\/s41467-023-39710-z","DOI":"10.1038\/s41467-023-39710-z"},{"key":"ref74","doi-asserted-by":"crossref","unstructured":"75.\tMarulanda-D\u00edaz N, Estrada-Restrepo A, Mil\u00e1n AF, Narvaez-Sanchez R, Calder\u00f3n JC, Giraldo-Giraldo NA. Relationship between myostatin, musclin, nutritional status and functionality in Colombian community-dwelling older adults: a cross-sectional study. Nutrition 2025;135:112767. https:\/\/doi.org\/10.1016\/j.nut.2025.112767","DOI":"10.1016\/j.nut.2025.112767"},{"key":"ref75","doi-asserted-by":"crossref","unstructured":"76. Nicola NA, Babon JJ. Leukemia inhibitory factor (LIF). Cytokine Growth Factor Rev 2015;26:533-544. https:\/\/doi.org\/10.1016\/j.cytogfr.2015.07.001","DOI":"10.1016\/j.cytogfr.2015.07.001"},{"key":"ref76","doi-asserted-by":"crossref","unstructured":"77.\tBroholm C, Laye MJ, Brandt C, Vadalasetty R, Pilegaard H, Pedersen BK, Scheele C. LIF is a contraction-induced myokine stimulating human myocyte proliferation. J Appl Physiol 2011;111:251-259. https:\/\/doi.org\/10.1152\/japplphysiol.01399.2010","DOI":"10.1152\/japplphysiol.01399.2010"},{"key":"ref77","doi-asserted-by":"crossref","unstructured":"78.\tSpangenburg EE, Booth FW. Multiple signaling pathways mediate LIF-induced skeletal muscle satellite cell proliferation. Am J Physiol Cell Physiol 2002;283:C204-C211. https:\/\/doi.org\/10.1152\/ajpcell.00574.2001","DOI":"10.1152\/ajpcell.00574.2001"},{"key":"ref78","doi-asserted-by":"crossref","unstructured":"79.\tSpangenburg EE, Booth FW. Leukemia inhibitory factor restores the hypertrophic response to increased loading in the LIF(\u2212\/\u2212) mouse. Cytokine 2006;34:125-130. https:\/\/doi.org\/10.1016\/j.cyto.2006.05.001","DOI":"10.1016\/j.cyto.2006.05.001"},{"key":"ref79","doi-asserted-by":"crossref","unstructured":"80.\tBarnard W, Bower J, Brown MA, Murphy M, Austin L. Leukemia inhibitory factor (LIF) infusion stimulates skeletal muscle regeneration after injury: Injured muscle expresses lif mRNA. J Neurol Sci 1994;123:108-113. https:\/\/doi.org\/10.1016\/0022-510X(94)90211-9","DOI":"10.1016\/0022-510X(94)90211-9"},{"key":"ref80","doi-asserted-by":"crossref","unstructured":"81.\tWelc SS, Flores I, Wehling-Henricks M, Ramos J, Wang Y, Bertoni C, Tidball JG. Targeting a therapeutic LIF transgene to muscle via the immune system ameliorates muscular dystrophy. Nat Commun 2019;10:2788. https:\/\/doi.org\/10.1038\/s41467-019-10614-1","DOI":"10.1038\/s41467-019-10614-1"},{"key":"ref81","doi-asserted-by":"crossref","unstructured":"82.\tArora GK, Gupta A, Narayanan S, Guo T, Iyengar P, Infante RE. Cachexia-associated adipose loss induced by tumor-secreted leukemia inhibitory factor is counterbalanced by decreased leptin. JCI Insight 2018;3:e121221. https:\/\/doi.org\/10.1172\/jci.insight.121221","DOI":"10.1172\/jci.insight.121221"},{"key":"ref82","doi-asserted-by":"crossref","unstructured":"83.\tGuo T, Gupta A, Yu J, Granados JZ, Gandhi AY, Evers BM, Iyengar P, et al. LIFR-\u03b1-dependent adipocyte signaling in obesity limits adipose expansion contributing to fatty liver disease. iScience 2021;24:102227. https:\/\/doi.org\/10.1016\/j.isci.2021.102227","DOI":"10.1016\/j.isci.2021.102227"},{"key":"ref83","doi-asserted-by":"crossref","unstructured":"84.\tOost LJ, Kustermann M, Armani A, Blaauw B, Romanello V. Fibroblast growth factor 21 controls mitophagy and muscle mass. J Cachexia Sarcopenia Muscle 2019;10:630-642. https:\/\/doi.org\/10.1002\/jcsm.12409","DOI":"10.1002\/jcsm.12409"},{"key":"ref84","doi-asserted-by":"crossref","unstructured":"85.\tLarson KR, Jayakrishnan D, Soto Sauza KA, Goodson ML, Chaffin AT, Davidyan A, et al. FGF21 Induces Skeletal Muscle Atrophy and Increases Amino Acids in Female Mice: A Potential Role for Glucocorticoids. Endocrinology 2024;165:bqae004. https:\/\/doi.org\/10.1210\/endocr\/bqae004","DOI":"10.1210\/endocr\/bqae004"},{"key":"ref85","doi-asserted-by":"crossref","unstructured":"86.\tLuo X, Zhang H, Cao X, Yang D, Yan Y, Lu J, Wang X, Wang H. Endurance Exercise-Induced Fgf21 Promotes Skeletal Muscle Fiber Conversion through TGF-\u03b21 and p38 MAPK Signaling Pathway. Int J Mol Sci 2023;24:11401. https:\/\/doi.org\/10.3390\/ijms241411401","DOI":"10.3390\/ijms241411401"},{"key":"ref86","doi-asserted-by":"crossref","unstructured":"87.\tIeko T, Fujiki J, Hasegawa Y, Iwasaki T, Iwano H, Maeda N. Mechanism of skeletal muscle atrophy by muscle fiber types in male rats under long-term fasting stress. Steroids 2023;200:109328. https:\/\/doi.org\/10.1016\/j.steroids.2023.109328","DOI":"10.1016\/j.steroids.2023.109328"},{"key":"ref87","doi-asserted-by":"crossref","unstructured":"88.\tBonDurant LD, Ameka M, Naber MC, Markan KR, Idiga SO, Acevedo MR, Walsh SA, et al. FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms. Cell Metab 2017;25:935-944.e4. https:\/\/doi.org\/10.1016\/j.cmet.2017.03.005","DOI":"10.1016\/j.cmet.2017.03.005"},{"key":"ref88","doi-asserted-by":"crossref","unstructured":"89.\tSeverinsen MCK, Pedersen BK. Muscle-Organ Crosstalk: The Emerging Roles of Myokines. Endocr Rev 2020;41:594-609. https:\/\/doi.org\/10.1210\/endrev\/bnaa016","DOI":"10.1210\/endrev\/bnaa016"},{"key":"ref89","doi-asserted-by":"crossref","unstructured":"90.\tEllingsgaard H, Ehses JA, Hammar EB, Van Lommel L, Quintens R, Martens G, Kerr-Conte J, et al. Interleukin-6 regulates pancreatic \u03b1-cell mass expansion. Proc Natl Acad Sci U S A 2008;105:13163-13168. https:\/\/doi.org\/10.1073\/pnas.0801059105","DOI":"10.1073\/pnas.0801059105"},{"key":"ref90","doi-asserted-by":"crossref","unstructured":"91.\tFebbraio MA, Hiscock N, Sacchetti M, Fischer CP, Pedersen BK. Interleukin-6 Is a Novel Factor Mediating Glucose Homeostasis During Skeletal Muscle Contraction. Diabetes 2004;53:1643-1648. https:\/\/doi.org\/10.2337\/diabetes.53.7.1643","DOI":"10.2337\/diabetes.53.7.1643"},{"key":"ref91","doi-asserted-by":"crossref","unstructured":"92.\tBostr\u00f6m P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, et al. A PGC1-\u03b1-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012;481:463-468. https:\/\/doi.org\/10.1038\/nature10777","DOI":"10.1038\/nature10777"},{"key":"ref92","doi-asserted-by":"crossref","unstructured":"93.\tJiang S, Bae J-H, Wang Y, Song W. The Potential Roles of Myokines in Adipose Tissue Metabolism with Exercise and Cold Exposure. Int J Mol Sci 2022;23:11523. https:\/\/doi.org\/10.3390\/ijms231911523","DOI":"10.3390\/ijms231911523"},{"key":"ref93","doi-asserted-by":"crossref","unstructured":"94.\tLang Lehrskov L, Lyngbaek MP, Soederlund L, Legaard GE, Ehses JA, Heywood SE, Wewer Albrechtsen NJ, et al. Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control. Cell Metab 2018;27:1201-1211.e3. https:\/\/doi.org\/10.1016\/j.cmet.2018.04.008","DOI":"10.1016\/j.cmet.2018.04.008"},{"key":"ref94","doi-asserted-by":"crossref","unstructured":"95.\tMittenb\u00fchler MJ, Jedrychowski MP, Van Vranken JG, Sprenger H-G, Wilensky S, Dumesic PA, Sun Y, et al. Isolation of extracellular fluids reveals novel secreted bioactive proteins from muscle and fat tissues. Cell Metab 2023;35:535-549.e7. https:\/\/doi.org\/10.1016\/j.cmet.2022.12.014","DOI":"10.1016\/j.cmet.2022.12.014"},{"key":"ref95","doi-asserted-by":"crossref","unstructured":"96.\tLi F, Li Y, Duan Y, Hu C-AA, Tang Y, Yin Y. Myokines and adipokines: Involvement in the crosstalk between skeletal muscle and adipose tissue. Cytokine Growth Factor Rev 2017;33:73-82. https:\/\/doi.org\/10.1016\/j.cytogfr.2016.10.003","DOI":"10.1016\/j.cytogfr.2016.10.003"},{"key":"ref96","doi-asserted-by":"crossref","unstructured":"97.\tStanford KI, Goodyear LJ. Muscle-Adipose Tissue Cross Talk. Cold Spring Harb Perspect Med 2018;8:a029801. https:\/\/doi.org\/10.1101\/cshperspect.a029801","DOI":"10.1101\/cshperspect.a029801"},{"key":"ref97","doi-asserted-by":"crossref","unstructured":"98.\tMastrototaro L, Roden M. Insulin resistance and insulin sensitizing agents. Metabolism 2021;125:154892. https:\/\/doi.org\/10.1016\/j.metabol.2021.154892","DOI":"10.1016\/j.metabol.2021.154892"},{"key":"ref98","doi-asserted-by":"crossref","unstructured":"99.\tItoh N. FGF21 as a Hepatokine, Adipokine, and Myokine in Metabolism and Diseases. Front Endocrinol (Lausanne) 2014;5:107. https:\/\/doi.org\/10.3389\/fendo.2014.00107","DOI":"10.3389\/fendo.2014.00107"},{"key":"ref99","doi-asserted-by":"crossref","unstructured":"100.\tDeguchi E, Matsuda M, Terai K. Live imaging of paracrine signaling: Advances in visualization and tracking techniques. 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