Skip to main content

Advertisement

Log in

Implications of exercise-induced adipo-myokines in bone metabolism

  • Review
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Physical inactivity has been recognized, by the World Health Organization as the fourth cause of death (5.5 % worldwide). On the contrary, physical activity (PA) has been associated with improved quality of life and decreased risk of several diseases (i.e., stroke, hypertension, myocardial infarction, obesity, malignancies). Bone turnover is profoundly affected from PA both directly (load degree is the key determinant for BMD) and indirectly through the activation of several endocrine axes. Several molecules, secreted by muscle (myokines) and adipose tissues (adipokines) in response to exercise, are involved in the fine regulation of bone metabolism in response to the energy availability. Furthermore, bone regulates energy metabolism by communicating its energetic needs thanks to osteocalcin which acts on pancreatic β-cells and adipocytes. The beneficial effects of exercise on bone metabolism depends on the intermittent exposure to myokines (i.e., irisin, IL-6, LIF, IGF-I) which, instead, act as inflammatory/pro-resorptive mediators when chronically elevated; on the other hand, the reduction in the circulating levels of adipokines (i.e., leptin, visfatin, adiponectin, resistin) sustains these effects as well as improves the whole-body metabolic status. The aim of this review is to highlight the newest findings about the exercise-dependent regulation of these molecules and their role in the fine regulation of bone metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. H.B. Simon, Exercise and health: dose and response, considering both ends of the curve. Am. J. Med. 128(11), 1171–1177 (2015)

    Article  PubMed  Google Scholar 

  2. D. Bishop-Bailey, Mechanisms governing the health and performance benefits of exercise. Br. J. Pharmacol. 170(6), 1153–1166 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. M.P. Mattson, Evolutionary aspects of human exercise–born to run purposefully. Ageing Res. Rev. 11(3), 347–352 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. D.M. Bramble, D.E. Lieberman, Endurance running and the evolution of Homo. Nature 432(7015), 345–352 (2004)

    Article  CAS  PubMed  Google Scholar 

  5. World Health Organization, Global database on blood safety: report 2004–2005 (World Health Organization, Geneva, 2008)

    Google Scholar 

  6. G. Banfi, G. Lombardi, A. Colombini, G. Lippi, Bone metabolism markers in sports medicine. Sports Med. 40, 697–714 (2010)

    Article  PubMed  Google Scholar 

  7. A.D. DiVasta, C.M. Gordon, Exercise and bone: where do we stand? Metabolism 62(12), 1714–1717 (2013)

    Article  CAS  PubMed  Google Scholar 

  8. G. Lombardi, S. Perego, L. Luzi, G. Banfi, A four-season molecule: osteocalcin. Updates in its physiological roles. Endocrine 48, 394–404 (2015)

    Article  CAS  PubMed  Google Scholar 

  9. C.B. Confavreux, R.L. Levine, G. Karsenty, A paradigm of integrative physiology, the crosstalk between bone and energy metabolisms. Mol. Cell. Endocrinol. 310(1–2), 21–29 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. K.L. Scofield, S. Hecht, Bone health in endurance athletes: runners, cyclists, and swimmers. Curr Sports Med Rep 11(6), 328–334 (2012)

    Article  PubMed  Google Scholar 

  11. H. Olmedillas, A. Gonzalez-Aguero, L.A. Moreno, J.A. Casajus, G. Vicente-Rodriguez, Bone related health status in adolescent cyclists. PLoS ONE 6(9), e24841 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. M.R. Carmont, Bike racing, recreational riding, impact sport and bone health. BMC Med. 10, 169 (2012)

    Article  PubMed  PubMed Central  Google Scholar 

  13. H.C. Emslander, M. Sinaki, J.M. Muhs, E.Y. Chao, H.W. Wahner, S.C. Bryant, B.L. Riggs, R. Eastell, Bone mass and muscle strength in female college athletes (runners and swimmers). Mayo Clin. Proc. 73(12), 1151–1160 (1998)

    Article  CAS  PubMed  Google Scholar 

  14. C.S. Duncan, C.J. Blimkie, C.T. Cowell, S.T. Burke, J.N. Briody, R. Howman-Giles, Bone mineral density in adolescent female athletes: relationship to exercise type and muscle strength. Med. Sci. Sports Exerc. 34(2), 286–294 (2002)

    Article  PubMed  Google Scholar 

  15. R.S. Rector, R. Rogers, M. Ruebel, P.S. Hinton, Participation in road cycling vs running is associated with lower bone mineral density in men. Metabolism 57, 226–232 (2008)

    Article  CAS  PubMed  Google Scholar 

  16. G. Lombardi, P. Lanteri, G. Graziani, A. Colombini, G. Banfi, R. Corsetti, Bone and energy metabolism parameters in professional cyclists during the Giro d’Italia 3-weeks stage race. PLoS ONE 7(7), e42077 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. D. Grasso, R. Corsetti, P. Lanteri, C. Di Bernardo, A. Colombini, R. Graziani, G. Banfi, G. Lombardi, Bone-muscle unit activity, salivary steroid hormones profile, and physical effort over a 3-week stage race. Scand. J. Med. Sci. Sports 25(1), 70–80 (2015)

    Article  CAS  PubMed  Google Scholar 

  18. G. Lombardi, R. Corsetti, P. Lanteri, D. Grasso, E. Vianello, M.G. Marazzi, R. Graziani, A. Colombini, E. Galliera, M.M. Corsi Romanelli, G. Banfi, Reciprocal regulation of calcium-/phosphate-regulating hormones in cyclists during the Giro d’Italia 3-week stage race. Scand. J. Med. Sci. Sports 24(5), 779–787 (2014)

    Article  CAS  PubMed  Google Scholar 

  19. A. Colombini, R. Corsetti, R. Graziani, G. Lombardi, P. Lanteri, G. Banfi, Evaluation of creatinine, cystatin C and eGFR by different equations in professional cyclists during the Giro d’Italia 3-weeks stage race. Scand. J. Clin. Lab. Invest. 72(2), 114–120 (2012)

    Article  CAS  PubMed  Google Scholar 

  20. W. Qin, L. Sun, J. Cao, Y. Peng, L. Collier, Y. Wu, G. Creasey, J. Li, Y. Qin, J. Jarvis, W.A. Bauman, M. Zaidi, C. Cardozo, The central nervous system (CNS)-independent anti-bone-resorptive activity of muscle contraction and the underlying molecular and cellular signatures. J. Biol. Chem. 288(19), 13511–13521 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. G. Lombardi, A. Colombini, M. Freschi, R. Tavana, G. Banfi, Seasonal variation of bone turnover markers in top-level female skiers. Eur. J. Appl. Physiol. 111(3), 433–440 (2011)

    Article  PubMed  Google Scholar 

  22. N.S. Datta, Muscle-bone and fat-bone interactions in regulating bone mass: do PTH and PTHrP play any role? Endocrine 47(2), 389–400 (2014)

    Article  CAS  PubMed  Google Scholar 

  23. C. Cassell, M. Benedict, B. Specker, Bone mineral density in elite 7- to 9-yr-old female gymnasts and swimmers. Med. Sci. Sports Exerc. 28(10), 1243–1246 (1996)

    Article  CAS  PubMed  Google Scholar 

  24. S.S. Moon, Relationship of lean body mass with bone mass and bone mineral density in the general Korean population. Endocrine 47(1), 234–243 (2014)

    Article  CAS  PubMed  Google Scholar 

  25. A. Heinonen, P. Oja, P. Kannus, H. Sievanen, A. Manttari, I. Vuori, Bone mineral density of female athletes in different sports. Bone Miner. 23(1), 1–14 (1993)

    Article  CAS  PubMed  Google Scholar 

  26. M. Martyn-St James, S. Carroll, Effects of different impact exercise modalities on bone mineral density in premenopausal women: a meta-analysis. J. Bone Miner. Metab. 28(3), 251–267 (2010)

    Article  PubMed  Google Scholar 

  27. E.A. Marques, J. Mota, L. Machado, F. Sousa, M. Coelho, P. Moreira, J. Carvalho, Multicomponent training program with weight-bearing exercises elicits favorable bone density, muscle strength, and balance adaptations in older women. Calcif. Tissue Int. 88(2), 117–129 (2011)

    Article  CAS  PubMed  Google Scholar 

  28. L.M. Giangregorio, A. Papaioannou, N.J. Macintyre, M.C. Ashe, A. Heinonen, K. Shipp, J. Wark, S. McGill, H. Keller, R. Jain, J. Laprade, A.M. Cheung, Too fit to fracture: exercise recommendations for individuals with osteoporosis or osteoporotic vertebral fracture. Osteoporos. Int. 25(3), 821–835 (2014)

    Article  CAS  PubMed  Google Scholar 

  29. E.A. Marques, J. Mota, J.L. Viana, D. Tuna, P. Figueiredo, J.T. Guimaraes, J. Carvalho, Response of bone mineral density, inflammatory cytokines, and biochemical bone markers to a 32-week combined loading exercise programme in older men and women. Arch. Gerontol. Geriatr. 57(2), 226–233 (2013)

    Article  CAS  PubMed  Google Scholar 

  30. A. Heinonen, P. Oja, P. Kannus, H. Sievanen, H. Haapasalo, A. Manttari, I. Vuori, Bone mineral density in female athletes representing sports with different loading characteristics of the skeleton. Bone 17(3), 197–203 (1995)

    Article  CAS  PubMed  Google Scholar 

  31. M.P. Mosti, T. Carlsen, E. Aas, J. Hoff, A.K. Stunes, U. Syversen, Maximal strength training improves bone mineral density and neuromuscular performance in young adult women. J. Strength Cond. Res. 28(10), 2935–2945 (2014)

    Article  PubMed  Google Scholar 

  32. C.T. Rubin, Skeletal strain and the functional significance of bone architecture. Calcif. Tissue Int. 36(Suppl 1), S11–S18 (1984)

    Article  PubMed  Google Scholar 

  33. C.H. Turner, M.R. Forwood, M.W. Otter, Mechanotransduction in bone: do bone cells act as sensors of fluid flow? FASEB J. 8(11), 875–878 (1994)

    CAS  PubMed  Google Scholar 

  34. A.G. Robling, F.M. Hinant, D.B. Burr, C.H. Turner, Improved bone structure and strength after long-term mechanical loading is greatest if loading is separated into short bouts. J. Bone Miner. Res. 17(8), 1545–1554 (2002)

    Article  PubMed  Google Scholar 

  35. Y. Wang, L.M. McNamara, M.B. Schaffler, S. Weinbaum, Strain amplification and integrin based signaling in osteocytes. J. Musculoskelet. Neuronal Interact. 8(4), 332–334 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  36. T. Adachi, Y. Aonuma, M. Tanaka, M. Hojo, T. Takano-Yamamoto, H. Kamioka, Calcium response in single osteocytes to locally applied mechanical stimulus: differences in cell process and cell body. J. Biomech. 42(12), 1989–1995 (2009)

    Article  PubMed  Google Scholar 

  37. S. Tatsumi, K. Ishii, N. Amizuka, M. Li, T. Kobayashi, K. Kohno, M. Ito, S. Takeshita, K. Ikeda, Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 5(6), 464–475 (2007)

    Article  CAS  PubMed  Google Scholar 

  38. G.Y. Rochefort, S. Pallu, C.L. Benhamou, Osteocyte: the unrecognized side of bone tissue. Osteoporos. Int. 21(9), 1457–1469 (2010)

    Article  CAS  PubMed  Google Scholar 

  39. G. Colaianni, G. Brunetti, M.F. Faienza, S. Colucci, M. Grano, Osteoporosis and obesity: role of Wnt pathway in human and murine models. World J. Orthop. 5(3), 242–246 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  40. X. Li, M.S. Ominsky, Q.T. Niu, N. Sun, B. Daugherty, D. D’Agostin, C. Kurahara, Y. Gao, J. Cao, J. Gong, F. Asuncion, M. Barrero, K. Warmington, D. Dwyer, M. Stolina, S. Morony, I. Sarosi, P.J. Kostenuik, D.L. Lacey, W.S. Simonet, H.Z. Ke, C. Paszty, Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J. Bone Miner. Res. 23(6), 860–869 (2008)

    Article  PubMed  Google Scholar 

  41. P. Schwab, K. Scalapino, Exercise for bone health: rationale and prescription. Curr. Opin. Rheumatol. 23(2), 137–141 (2011)

    Article  PubMed  Google Scholar 

  42. A.M. Cheung, L. Giangregorio, Mechanical stimuli and bone health: what is the evidence? Curr. Opin. Rheumatol. 24(5), 561–566 (2012)

    Article  PubMed  Google Scholar 

  43. E. Ozcivici, Y.K. Luu, B. Adler, Y.X. Qin, J. Rubin, S. Judex, C.T. Rubin, Mechanical signals as anabolic agents in bone. Nat. Rev. Rheumatol. 6(1), 50–59 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. C.T. Rubin, E. Capilla, Y.K. Luu, B. Busa, H. Crawford, D.J. Nolan, V. Mittal, C.J. Rosen, J.E. Pessin, S. Judex, Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals. Proc. Natl. Acad. Sci. USA 104(45), 17879–17884 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Y.K. Luu, E. Capilla, C.J. Rosen, V. Gilsanz, J.E. Pessin, S. Judex, C.T. Rubin, Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J. Bone Miner. Res. 24(1), 50–61 (2009)

    Article  CAS  PubMed  Google Scholar 

  46. A.G. Robling, P.J. Niziolek, L.A. Baldridge, K.W. Condon, M.R. Allen, I. Alam, S.M. Mantila, J. Gluhak-Heinrich, T.M. Bellido, S.E. Harris, C.H. Turner, Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J. Biol. Chem. 283(9), 5866–5875 (2008)

    Article  CAS  PubMed  Google Scholar 

  47. N. Bonnet, K.N. Standley, E.N. Bianchi, V. Stadelmann, M. Foti, S.J. Conway, S.L. Ferrari, The matricellular protein periostin is required for sost inhibition and the anabolic response to mechanical loading and physical activity. J. Biol. Chem. 284(51), 35939–35950 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. K. Amrein, S. Amrein, C. Drexler, H.P. Dimai, H. Dobnig, K. Pfeifer, A. Tomaschitz, T.R. Pieber, A. Fahrleitner-Pammer, Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults. J. Clin. Endocrinol. Metab. 97(1), 148–154 (2012)

    Article  CAS  PubMed  Google Scholar 

  49. G. Lombardi, P. Lanteri, A. Colombini, M. Mariotti, G. Banfi, Sclerostin concentrations in athletes: role of load and gender. J. Biol. Regul. Homeost. Agents 26(1), 157–163 (2012)

    CAS  PubMed  Google Scholar 

  50. J. Jurimae, V. Tillmann, A. Cicchella, C. Stefanelli, K. Vosoberg, A.L. Tamm, T. Jurimae, Increased sclerostin and preadipocyte factor-1 levels in prepubertal rhythmic gymnasts: associations with bone mineral density, body composition, and adipocytokine values. Osteoporos. Int. (2015). doi:10.1007/s00198-015-3301-0

    PubMed  Google Scholar 

  51. L.B. Meakin, C. Udeh, G.L. Galea, L.E. Lanyon, J.S. Price, Exercise does not enhance aged bone’s impaired response to artificial loading in C57Bl/6 mice. Bone 81, 47–52 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  52. K. Kerschan-Schindl, M.M. Thalmann, E. Weiss, M. Tsironi, U. Foger-Samwald, J. Meinhart, K. Skenderi, P. Pietschmann, Changes in Serum Levels of Myokines and Wnt-Antagonists after an Ultramarathon Race. PLoS ONE 10(7), e0132478 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. D.L. Belavy, N. Baecker, G. Armbrecht, G. Beller, J. Buehlmeier, P. Frings-Meuthen, J. Rittweger, H.J. Roth, M. Heer, D. Felsenberg, Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest. J. Bone Miner. Metab. (2015). doi:10.1007/s00774-015-0681-3

    PubMed  Google Scholar 

  54. I. Bergstrom, P. Parini, S.A. Gustafsson, G. Andersson, J. Brinck, Physical training increases osteoprotegerin in postmenopausal women. J. Bone Miner. Metab. 30(2), 202–207 (2012)

    Article  PubMed  CAS  Google Scholar 

  55. J.L. Ferretti, R.F. Capozza, G.R. Cointry, S.L. Garcia, H. Plotkin, M.L. Alvarez Filgueira, J.R. Zanchetta, Gender-related differences in the relationship between densitometric values of whole-body bone mineral content and lean body mass in humans between 2 and 87 years of age. Bone 22(6), 683–690 (1998)

    Article  CAS  PubMed  Google Scholar 

  56. L.H. Bogl, A. Latvala, J. Kaprio, O. Sovijarvi, A. Rissanen, K.H. Pietilainen, An investigation into the relationship between soft tissue body composition and bone mineral density in a young adult twin sample. J. Bone Miner. Res. 26(1), 79–87 (2011)

    Article  PubMed  Google Scholar 

  57. J. Rittweger, G. Beller, J. Ehrig, C. Jung, U. Koch, J. Ramolla, F. Schmidt, D. Newitt, S. Majumdar, H. Schiessl, D. Felsenberg, Bone-muscle strength indices for the human lower leg. Bone 27(2), 319–326 (2000)

    Article  CAS  PubMed  Google Scholar 

  58. E. Schoenau, From mechanostat theory to development of the “Functional Muscle-Bone-Unit”. J. Musculoskelet. Neuronal Interact. 5(3), 232–238 (2005)

    CAS  PubMed  Google Scholar 

  59. F. Rauch, D.A. Bailey, A. Baxter-Jones, R. Mirwald, R. Faulkner, The ‘muscle-bone unit’ during the pubertal growth spurt. Bone 34(5), 771–775 (2004)

    Article  PubMed  Google Scholar 

  60. T. Matsuoka, P.E. Ahlberg, N. Kessaris, P. Iannarelli, U. Dennehy, W.D. Richardson, A.P. McMahon, G. Koentges, Neural crest origins of the neck and shoulder. Nature 436(7049), 347–355 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. H.M. Frost, E. Schonau, The “muscle-bone unit” in children and adolescents: a 2000 overview. J. Pediatr. Endocrinol. Metab. 13(6), 571–590 (2000)

    Article  CAS  PubMed  Google Scholar 

  62. C. Tagliaferri, Y. Wittrant, M.J. Davicco, S. Walrand, V. Coxam, Muscle and bone, two interconnected tissues. Ageing Res. Rev. 21, 55–70 (2015)

    Article  CAS  PubMed  Google Scholar 

  63. L. Cianferotti, M.L. Brandi, Muscle-bone interactions: basic and clinical aspects. Endocrine 45(2), 165–177 (2014)

    Article  CAS  PubMed  Google Scholar 

  64. C. Gomez, V. David, N.M. Peet, L. Vico, C. Chenu, L. Malaval, T.M. Skerry, Absence of mechanical loading in utero influences bone mass and architecture but not innervation in Myod-Myf5-deficient mice. J. Anat. 210(3), 259–271 (2007)

    Article  PubMed  PubMed Central  Google Scholar 

  65. Y. Bren-Mattison, M. Hausburg, B.B. Olwin, Growth of limb muscle is dependent on skeletal-derived Indian hedgehog. Dev. Biol. 356(2), 486–495 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. A. Sharir, T. Stern, C. Rot, R. Shahar, E. Zelzer, Muscle force regulates bone shaping for optimal load-bearing capacity during embryogenesis. Development 138(15), 3247–3259 (2011)

    Article  CAS  PubMed  Google Scholar 

  67. N.C. Nowlan, J. Sharpe, K.A. Roddy, P.J. Prendergast, P. Murphy, Mechanobiology of embryonic skeletal development: insights from animal models. Birth Defects Res. C Embryo Today 90(3), 203–213 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. J. Kahn, Y. Shwartz, E. Blitz, S. Krief, A. Sharir, D.A. Breitel, R. Rattenbach, F. Relaix, P. Maire, R.B. Rountree, D.M. Kingsley, E. Zelzer, Muscle contraction is necessary to maintain joint progenitor cell fate. Dev. Cell 16(5), 734–743 (2009)

    Article  CAS  PubMed  Google Scholar 

  69. S.I. Zacks, M.F. Sheff, Periosteal and metaplastic bone formation in mouse minced muscle regeneration. Lab. Invest. 46(4), 405–412 (1982)

    CAS  PubMed  Google Scholar 

  70. S.E. Utvag, O. Grundnes, D.B. Rindal, O. Reikeras, Influence of extensive muscle injury on fracture healing in rat tibia. J. Orthop. Trauma 17(6), 430–435 (2003)

    Article  PubMed  Google Scholar 

  71. H. Kaufman, A. Reznick, H. Stein, M. Barak, G. Maor, The biological basis of the bone-muscle inter-relationship in the algorithm of fracture healing. Orthopedics 31(8), 751 (2008)

    Article  CAS  PubMed  Google Scholar 

  72. M.W. Hamrick, X. Shi, W. Zhang, C. Pennington, H. Thakore, M. Haque, B. Kang, C.M. Isales, S. Fulzele, K.H. Wenger, Loss of myostatin (GDF8) function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading. Bone 40(6), 1544–1553 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. M.R. Morissette, J.C. Stricker, M.A. Rosenberg, C. Buranasombati, E.B. Levitan, M.A. Mittleman, A. Rosenzweig, Effects of myostatin deletion in aging mice. Aging Cell 8(5), 573–583 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. M.E. Chan, B.J. Adler, D.E. Green, C.T. Rubin, Bone structure and B-cell populations, crippled by obesity, are partially rescued by brief daily exposure to low-magnitude mechanical signals. FASEB J. 26(12), 4855–4863 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. A. Seabra, E. Marques, J. Brito, P. Krustrup, S. Abreu, J. Oliveira, C. Rego, J. Mota, A. Rebelo, Muscle strength and soccer practice as major determinants of bone mineral density in adolescents. Joint Bone Spine 79(4), 403–408 (2012)

    Article  PubMed  Google Scholar 

  76. P. Krustrup, P.R. Hansen, L.J. Andersen, M.D. Jakobsen, E. Sundstrup, M.B. Randers, L. Christiansen, E.W. Helge, M.T. Pedersen, P. Sogaard, A. Junge, J. Dvorak, P. Aagaard, J. Bangsbo, Long-term musculoskeletal and cardiac health effects of recreational football and running for premenopausal women. Scand. J. Med. Sci. Sports 20(Suppl 1), 58–71 (2010)

    Article  PubMed  Google Scholar 

  77. E. Ozcivici, Y.K. Luu, C.T. Rubin, S. Judex, Low-level vibrations retain bone marrow’s osteogenic potential and augment recovery of trabecular bone during reambulation. PLoS ONE 5(6), e11178 (2010)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. J. Rittweger, H.M. Frost, H. Schiessl, H. Ohshima, B. Alkner, P. Tesch, D. Felsenberg, Muscle atrophy and bone loss after 90 days’ bed rest and the effects of flywheel resistive exercise and pamidronate: results from the LTBR study. Bone 36(6), 1019–1029 (2005)

    Article  PubMed  Google Scholar 

  79. J. Nam, P. Perera, R. Gordon, Y.H. Jeong, A.D. Blazek, D.G. Kim, B.C. Tee, Z. Sun, T.D. Eubank, Y. Zhao, B. Lablebecioglu, S. Liu, A. Litsky, N.L. Weisleder, B.S. Lee, T. Butterfield, A.L. Schneyer, S. Agarwal, Follistatin-like 3 is a mediator of exercise-driven bone formation and strengthening. Bone 78, 62–70 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. E. Assier, M.C. Boissier, J.M. Dayer, Interleukin-6: from identification of the cytokine to development of targeted treatments. Joint Bone Spine 77(6), 532–536 (2010)

    Article  CAS  PubMed  Google Scholar 

  81. B.K. Pedersen, Muscles and their myokines. J. Exp. Biol. 214(Pt 2), 337–346 (2011)

    Article  CAS  PubMed  Google Scholar 

  82. B.K. Pedersen, M.A. Febbraio, Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol. Rev. 88(4), 1379–1406 (2008)

    Article  CAS  PubMed  Google Scholar 

  83. M.A. Febbraio, P. Ott, H.B. Nielsen, A. Steensberg, C. Keller, P. Krustrup, N.H. Secher, B.K. Pedersen, Hepatosplanchnic clearance of interleukin-6 in humans during exercise. Am. J. Physiol. Endocrinol. Metab. 285(2), E397–E402 (2003)

    Article  CAS  PubMed  Google Scholar 

  84. A.L. Serrano, B. Baeza-Raja, E. Perdiguero, M. Jardi, P. Munoz-Canoves, Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. 7(1), 33–44 (2008)

    Article  CAS  PubMed  Google Scholar 

  85. T.A. Washington, J.P. White, J.M. Davis, L.B. Wilson, L.L. Lowe, S. Sato, J.A. Carson, Skeletal muscle mass recovery from atrophy in IL-6 knockout mice. Acta Physiol. (Oxf.) 202(4), 657–669 (2011)

    Article  CAS  PubMed Central  Google Scholar 

  86. J.M. Peake, P. Della Gatta, K. Suzuki, D.C. Nieman, Cytokine expression and secretion by skeletal muscle cells: regulatory mechanisms and exercise effects. Exerc. Immunol. Rev. 21, 8–25 (2015)

    PubMed  Google Scholar 

  87. C.P. Fischer, Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc. Immunol. Rev. 12, 6–33 (2006)

    PubMed  Google Scholar 

  88. G. Banfi, A. Colombini, G. Lombardi, A. Lubkowska, Metabolic markers in sports medicine. Adv. Clin. Chem. 56, 1–54 (2012)

    Article  CAS  PubMed  Google Scholar 

  89. S.L. Nehlsen-Cannarella, O.R. Fagoaga, D.C. Nieman, D.A. Henson, D.E. Butterworth, R.L. Schmitt, E.M. Bailey, B.J. Warren, A. Utter, J.M. Davis, Carbohydrate and the cytokine response to 2.5 h of running. J. Appl. Physiol. 82(5), 1662–1667 (1997)

    CAS  PubMed  Google Scholar 

  90. H. Ullum, P.M. Haahr, M. Diamant, J. Palmo, J. Halkjaer-Kristensen, B.K. Pedersen, Bicycle exercise enhances plasma IL-6 but does not change IL-1 alpha, IL-1 beta, IL-6, or TNF-alpha pre-mRNA in BMNC. J. Appl. Physiol. 77(1), 93–97 (1994)

    CAS  PubMed  Google Scholar 

  91. R.L. Starkie, D.J. Angus, J. Rolland, M. Hargreaves, M.A. Febbraio, Effect of prolonged, submaximal exercise and carbohydrate ingestion on monocyte intracellular cytokine production in humans. J. Physiol. 528(Pt 3), 647–655 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. R.L. Starkie, J. Rolland, D.J. Angus, M.J. Anderson, M.A. Febbraio, Circulating monocytes are not the source of elevations in plasma IL-6 and TNF-alpha levels after prolonged running. Am. J. Physiol. Cell Physiol. 280(4), C769–C774 (2001)

    CAS  PubMed  Google Scholar 

  93. C. Keller, Y. Hellsten, A. Steensberg, B.K. Pedersen, Differential regulation of IL-6 and TNF-alpha via calcineurin in human skeletal muscle cells. Cytokine 36(3–4), 141–147 (2006)

    Article  CAS  PubMed  Google Scholar 

  94. B.K. Pedersen, Muscular interleukin-6 and its role as an energy sensor. Med. Sci. Sports Exerc. 44(3), 392–396 (2012)

    Article  CAS  PubMed  Google Scholar 

  95. B.K. Pedersen, A. Steensberg, C. Fischer, C. Keller, P. Keller, P. Plomgaard, E. Wolsk-Petersen, M. Febbraio, The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor? Proc. Nutr. Soc. 63(2), 263–267 (2004)

    Article  CAS  PubMed  Google Scholar 

  96. N.B. Ruderman, C. Keller, A.M. Richard, A.K. Saha, Z. Luo, X. Xiang, M. Giralt, V.B. Ritov, E.V. Menshikova, D.E. Kelley, J. Hidalgo, B.K. Pedersen, M. Kelly, Interleukin-6 regulation of AMP-activated protein kinase. Potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes 55(Suppl 2), S48–S54 (2006)

    Article  CAS  PubMed  Google Scholar 

  97. M.A. Febbraio, A. Steensberg, C. Keller, R.L. Starkie, H.B. Nielsen, P. Krustrup, P. Ott, N.H. Secher, B.K. Pedersen, Glucose ingestion attenuates interleukin-6 release from contracting skeletal muscle in humans. J. Physiol. 549(Pt 2), 607–612 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. C.P. Fischer, P. Plomgaard, A.K. Hansen, H. Pilegaard, B. Saltin, B.K. Pedersen, Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 287(6), E1189–E1194 (2004)

    Article  CAS  PubMed  Google Scholar 

  99. M. De Lisio, G. Parise, Characterization of the effects of exercise training on hematopoietic stem cell quantity and function. J. Appl. Physiol. 113(10), 1576–1584 (2012)

    Article  PubMed  PubMed Central  Google Scholar 

  100. C. Keller, A. Steensberg, A.K. Hansen, C.P. Fischer, P. Plomgaard, B.K. Pedersen, Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle. J. Appl. Physiol. 99(6), 2075–2079 (2005)

    Article  CAS  PubMed  Google Scholar 

  101. B.K. Pedersen, M.A. Febbraio, Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat. Rev. Endocrinol. 8(8), 457–465 (2012)

    Article  CAS  PubMed  Google Scholar 

  102. A.L. Carey, G.R. Steinberg, S.L. Macaulay, W.G. Thomas, A.G. Holmes, G. Ramm, O. Prelovsek, C. Hohnen-Behrens, M.J. Watt, D.E. James, B.E. Kemp, B.K. Pedersen, M.A. Febbraio, Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 55(10), 2688–2697 (2006)

    Article  CAS  PubMed  Google Scholar 

  103. G. van Hall, A. Steensberg, M. Sacchetti, C. Fischer, C. Keller, P. Schjerling, N. Hiscock, K. Moller, B. Saltin, M.A. Febbraio, B.K. Pedersen, Interleukin-6 stimulates lipolysis and fat oxidation in humans. J. Clin. Endocrinol. Metab. 88(7), 3005–3010 (2003)

    Article  PubMed  CAS  Google Scholar 

  104. C.R. Bruce, D.J. Dyck, Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-alpha. Am. J. Physiol. Endocrinol. Metab. 287(4), E616–621 (2004)

    Article  CAS  PubMed  Google Scholar 

  105. B.B. Kahn, T. Alquier, D. Carling, D.G. Hardie, AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 1(1), 15–25 (2005)

    Article  CAS  PubMed  Google Scholar 

  106. S.M. Phillips, H.J. Green, M.A. Tarnopolsky, G.F. Heigenhauser, R.E. Hill, S.M. Grant, Effects of training duration on substrate turnover and oxidation during exercise. J. Appl. Physiol. 81(5), 2182–2191 (1996)

    CAS  PubMed  Google Scholar 

  107. M.A. Febbraio, N. Hiscock, M. Sacchetti, C.P. Fischer, B.K. Pedersen, Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction. Diabetes 53(7), 1643–1648 (2004)

    Article  CAS  PubMed  Google Scholar 

  108. G.R. Steinberg, M.J. Watt, M.A. Febbraio, Cytokine Regulation of AMPK signalling. Front. Biosci. (Landmark Ed.) 14, 1902–1916 (2009)

    Article  CAS  Google Scholar 

  109. M.J. Watt, N. Dzamko, W.G. Thomas, S. Rose-John, M. Ernst, D. Carling, B.E. Kemp, M.A. Febbraio, G.R. Steinberg, CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat. Med. 12(5), 541–548 (2006)

    Article  CAS  PubMed  Google Scholar 

  110. V. Wallenius, K. Wallenius, B. Ahren, M. Rudling, H. Carlsten, S.L. Dickson, C. Ohlsson, J.O. Jansson, Interleukin-6-deficient mice develop mature-onset obesity. Nat. Med. 8(1), 75–79 (2002)

    Article  CAS  PubMed  Google Scholar 

  111. S. Nielsen, B.K. Pedersen, Skeletal muscle as an immunogenic organ. Curr. Opin. Pharmacol. 8(3), 346–351 (2008)

    Article  CAS  PubMed  Google Scholar 

  112. A.M. Petersen, B.K. Pedersen, The anti-inflammatory effect of exercise. J. Appl. Physiol. 98(4), 1154–1162 (2005)

    Article  CAS  PubMed  Google Scholar 

  113. R.L. Jilka, G. Hangoc, G. Girasole, G. Passeri, D.C. Williams, J.S. Abrams, B. Boyce, H. Broxmeyer, S.C. Manolagas, Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science 257(5066), 88–91 (1992)

    Article  CAS  PubMed  Google Scholar 

  114. B. Le Goff, F. Blanchard, J.M. Berthelot, D. Heymann, Y. Maugars, Role for interleukin-6 in structural joint damage and systemic bone loss in rheumatoid arthritis. Joint Bone Spine 77(3), 201–205 (2010)

    Article  PubMed  CAS  Google Scholar 

  115. R. Axmann, C. Bohm, G. Kronke, J. Zwerina, J. Smolen, G. Schett, Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo. Arthritis Rheum. 60(9), 2747–2756 (2009)

    Article  CAS  PubMed  Google Scholar 

  116. P. Palmqvist, E. Persson, H.H. Conaway, U.H. Lerner, IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae. J. Immunol. 169(6), 3353–3362 (2002)

    Article  CAS  PubMed  Google Scholar 

  117. N. Saidenberg-Kermanac’h, M. Cohen-Solal, N. Bessis, M.C. De Vernejoul, M.C. Boissier, Role for osteoprotegerin in rheumatoid inflammation. Joint Bone Spine 71(1), 9–13 (2004)

    Article  PubMed  Google Scholar 

  118. F. De Benedetti, P. Pignatti, M. Vivarelli, C. Meazza, G. Ciliberto, R. Savino, A. Martini, In vivo neutralization of human IL-6 (hIL-6) achieved by immunization of hIL-6-transgenic mice with a hIL-6 receptor antagonist. J. Immunol. 166(7), 4334–4340 (2001)

    Article  PubMed  Google Scholar 

  119. P.K. Wong, J.M. Quinn, N.A. Sims, A. van Nieuwenhuijze, I.K. Campbell, I.P. Wicks, Interleukin-6 modulates production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis Rheum. 54(1), 158–168 (2006)

    Article  CAS  PubMed  Google Scholar 

  120. Y.A. Mezil, D. Allison, K. Kish, D. Ditor, W.E. Ward, E. Tsiani, P. Klentrou, Response of bone turnover markers and cytokines to high-intensity low-impact exercise. Med. Sci. Sports Exerc. 47(7), 1495–1502 (2015)

    Article  CAS  PubMed  Google Scholar 

  121. E. Galliera, G. Lombardi, M.G. Marazzi, D. Grasso, E. Vianello, R. Pozzoni, G. Banfi, M.M. Corsi Romanelli, Acute exercise in elite rugby players increases the circulating level of the cardiovascular biomarker GDF-15. Scand. J. Clin. Lab. Invest. 74(6), 492–499 (2014)

    Article  CAS  PubMed  Google Scholar 

  122. R.K. Evans, A.J. Antczak, M. Lester, R. Yanovich, E. Israeli, D.S. Moran, Effects of a 4-month recruit training program on markers of bone metabolism. Med. Sci. Sports Exerc. 40(11 Suppl), S660–S670 (2008)

    Article  CAS  PubMed  Google Scholar 

  123. L. Li, X. Chen, S. Lv, M. Dong, L. Zhang, J. Tu, J. Yang, L. Zhang, Y. Song, L. Xu, J. Zou, Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis. PLoS ONE 9(11), e112845 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. L. Aguirre, N. Napoli, D. Waters, C. Qualls, D.T. Villareal, R. Armamento-Villareal, Increasing adiposity is associated with higher adipokine levels and lower bone mineral density in obese older adults. J. Clin. Endocrinol. Metab. 99(9), 3290–3297 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. J.H. Park, K.H. Park, S. Cho, Y.S. Choi, S.K. Seo, B.S. Lee, H.S. Park, Concomitant increase in muscle strength and bone mineral density with decreasing IL-6 levels after combination therapy with alendronate and calcitriol in postmenopausal women. Menopause 20(7), 747–753 (2013)

    Article  PubMed  Google Scholar 

  126. F. Haugen, F. Norheim, H. Lian, A.J. Wensaas, S. Dueland, O. Berg, A. Funderud, B.S. Skalhegg, T. Raastad, C.A. Drevon, IL7 is expressed and secreted by human skeletal muscle cells. Am. J. Physiol. Cell Physiol. 298(4), 807–816 (2010)

    Article  CAS  Google Scholar 

  127. R. Zhao, Immune regulation of osteoclast function in postmenopausal osteoporosis: a critical interdisciplinary perspective. Int. J. Med. Sci. 9(9), 825–832 (2012)

    Article  PubMed  PubMed Central  Google Scholar 

  128. S.K. Lee, C.D. Surh, Role of interleukin-7 in bone and T-cell homeostasis. Immunol. Rev. 208, 169–180 (2005)

    Article  CAS  PubMed  Google Scholar 

  129. M.N. Weitzmann, S. Cenci, L. Rifas, C. Brown, R. Pacifici, Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. Blood 96(5), 1873–1878 (2000)

    CAS  PubMed  Google Scholar 

  130. G. Toraldo, C. Roggia, W.P. Qian, R. Pacifici, M.N. Weitzmann, IL-7 induces bone loss in vivo by induction of receptor activator of nuclear factor kappa B ligand and tumor necrosis factor alpha from T cells. Proc. Natl. Acad. Sci. USA 100(1), 125–130 (2003)

    Article  CAS  PubMed  Google Scholar 

  131. D.G. Remick, Interleukin-8. Crit. Care Med. 33(12 Suppl), S466–S467 (2005)

    Article  PubMed  Google Scholar 

  132. T.J. Standiford, S.L. Kunkel, M.A. Basha, S.W. Chensue, J.P. Lynch 3rd, G.B. Toews, J. Westwick, R.M. Strieter, Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung. J. Clin. Invest. 86(6), 1945–1953 (1990)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. S. Apostolakis, K. Vogiatzi, V. Amanatidou, D.A. Spandidos, Interleukin 8 and cardiovascular disease. Cardiovasc. Res. 84(3), 353–360 (2009)

    Article  CAS  PubMed  Google Scholar 

  134. D.C. Nieman, J.M. Davis, D.A. Henson, S.J. Gross, C.L. Dumke, A.C. Utter, D.M. Vinci, J.A. Carson, A. Brown, S.R. McAnulty, L.S. McAnulty, N.T. Triplett, Muscle cytokine mRNA changes after 2.5 h of cycling: influence of carbohydrate. Med. Sci. Sports Exerc. 37(8), 1283–1290 (2005)

    Article  CAS  PubMed  Google Scholar 

  135. E. Goussetis, A. Spiropoulos, M. Tsironi, K. Skenderi, A. Margeli, S. Graphakos, P. Baltopoulos, I. Papassotiriou, Spartathlon, a 246 kilometer foot race: effects of acute inflammation induced by prolonged exercise on circulating progenitor reparative cells. Blood Cells Mol. Dis. 42(3), 294–299 (2009)

    Article  CAS  PubMed  Google Scholar 

  136. K. Suzuki, S. Nakaji, M. Yamada, Q. Liu, S. Kurakake, N. Okamura, T. Kumae, T. Umeda, K. Sugawara, Impact of a competitive marathon race on systemic cytokine and neutrophil responses. Med. Sci. Sports Exerc. 35(2), 348–355 (2003)

    Article  CAS  PubMed  Google Scholar 

  137. L. Malaval, J.E. Aubin, Biphasic effects of leukemia inhibitory factor on osteoblastic differentiation. J. Cell Biochem. Suppl. 36, 63–70 (2001)

    Article  PubMed  Google Scholar 

  138. C. Broholm, O.H. Mortensen, S. Nielsen, T. Akerstrom, A. Zankari, B. Dahl, B.K. Pedersen, Exercise induces expression of leukaemia inhibitory factor in human skeletal muscle. J. Physiol. 586(8), 2195–2201 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. N.A. Sims, R.W. Johnson, Leukemia inhibitory factor: a paracrine mediator of bone metabolism. Growth Factors 30(2), 76–87 (2012)

    Article  CAS  PubMed  Google Scholar 

  140. L. Laviola, A. Natalicchio, F. Giorgino, The IGF-I signaling pathway. Curr. Pharm. Des. 13(7), 663–669 (2007)

    Article  CAS  PubMed  Google Scholar 

  141. A. Giustina, G. Mazziotti, E. Canalis, Growth hormone, insulin-like growth factors, and the skeleton. Endocr. Rev. 29(5), 535–559 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. D. Le Roith, C. Bondy, S. Yakar, J.L. Liu, A. Butler, The somatomedin hypothesis: 2001. Endocr. Rev. 22(1), 53–74 (2001)

    Article  PubMed  Google Scholar 

  143. C. Ohlsson, A. Nilsson, O. Isaksson, A. Lindahl, Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate. Proc. Natl. Acad. Sci. USA 89(20), 9826–9830 (1992)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. T.L. McCarthy, M. Centrella, E. Canalis, Cyclic AMP induces insulin-like growth factor I synthesis in osteoblast-enriched cultures. J. Biol. Chem. 265(26), 15353–15356 (1990)

    CAS  PubMed  Google Scholar 

  145. M. Ernst, G.A. Rodan, Estradiol regulation of insulin-like growth factor-I expression in osteoblastic cells: evidence for transcriptional control. Mol. Endocrinol. 5(8), 1081–1089 (1991)

    Article  CAS  PubMed  Google Scholar 

  146. M. Kassem, R. Okazaki, S.A. Harris, T.C. Spelsberg, C.A. Conover, B.L. Riggs, Estrogen effects on insulin-like growth factor gene expression in a human osteoblastic cell line with high levels of estrogen receptor. Calcif. Tissue Int. 62(1), 60–66 (1998)

    Article  CAS  PubMed  Google Scholar 

  147. A.M. Delany, D. Durant, E. Canalis, Glucocorticoid suppression of IGF I transcription in osteoblasts. Mol. Endocrinol. 15(10), 1781–1789 (2001)

    Article  CAS  PubMed  Google Scholar 

  148. P. Lakatos, M.D. Caplice, V. Khanna, P.H. Stern, Thyroid hormones increase insulin-like growth factor I content in the medium of rat bone tissue. J. Bone Miner. Res. 8(12), 1475–1481 (1993)

    Article  CAS  PubMed  Google Scholar 

  149. B.K. Huang, L.A. Golden, G. Tarjan, L.D. Madison, P.H. Stern, Insulin-like growth factor I production is essential for anabolic effects of thyroid hormone in osteoblasts. J. Bone Miner. Res. 15(2), 188–197 (2000)

    Article  CAS  PubMed  Google Scholar 

  150. E. Canalis, J. Pash, B. Gabbitas, S. Rydziel, S. Varghese, Growth factors regulate the synthesis of insulin-like growth factor-I in bone cell cultures. Endocrinology 133(1), 33–38 (1993)

    CAS  PubMed  Google Scholar 

  151. E. Canalis, A.N. Economides, E. Gazzerro, Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr. Rev. 24(2), 218–235 (2003)

    Article  CAS  PubMed  Google Scholar 

  152. E. Canalis, Effect of insulinlike growth factor I on DNA and protein synthesis in cultured rat calvaria. J. Clin. Invest. 66(4), 709–719 (1980)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. T.L. McCarthy, M. Centrella, E. Canalis, Regulatory effects of insulin-like growth factors I and II on bone collagen synthesis in rat calvarial cultures. Endocrinology 124(1), 301–309 (1989)

    Article  CAS  PubMed  Google Scholar 

  154. T. Thomas, F. Gori, T.C. Spelsberg, S. Khosla, B.L. Riggs, C.A. Conover, Response of bipotential human marrow stromal cells to insulin-like growth factors: effect on binding protein production, proliferation, and commitment to osteoblasts and adipocytes. Endocrinology 140(11), 5036–5044 (1999)

    CAS  PubMed  Google Scholar 

  155. M.P. Playford, D. Bicknell, W.F. Bodmer, V.M. Macaulay, Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. Proc. Natl. Acad. Sci. USA 97(22), 12103–12108 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. V. Krishnan, H.U. Bryant, O.A. Macdougald, Regulation of bone mass by Wnt signaling. J. Clin. Invest. 116(5), 1202–1209 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. H. Mochizuki, Y. Hakeda, N. Wakatsuki, N. Usui, S. Akashi, T. Sato, K. Tanaka, M. Kumegawa, Insulin-like growth factor-I supports formation and activation of osteoclasts. Endocrinology 131(3), 1075–1080 (1992)

    CAS  PubMed  Google Scholar 

  158. P. Hou, T. Sato, W. Hofstetter, N.T. Foged, Identification and characterization of the insulin-like growth factor I receptor in mature rabbit osteoclasts. J. Bone Miner. Res. 12(4), 534–540 (1997)

    Article  CAS  PubMed  Google Scholar 

  159. T. Niu, C.J. Rosen, The insulin-like growth factor-I gene and osteoporosis: a critical appraisal. Gene 361, 38–56 (2005)

    Article  CAS  PubMed  Google Scholar 

  160. T. Moriwake, H. Tanaka, S. Kanzaki, J. Higuchi, Y. Seino, 1,25-Dihydroxyvitamin D3 stimulates the secretion of insulin-like growth factor binding protein 3 (IGFBP-3) by cultured human osteosarcoma cells. Endocrinology 130(2), 1071–1073 (1992)

    CAS  PubMed  Google Scholar 

  161. K. Rajkumar, D. Barron, M.S. Lewitt, L.J. Murphy, Growth retardation and hyperglycemia in insulin-like growth factor binding protein-1 transgenic mice. Endocrinology 136(9), 4029–4034 (1995)

    CAS  PubMed  Google Scholar 

  162. V.E. DeMambro, D.R. Clemmons, L.G. Horton, M.L. Bouxsein, T.L. Wood, W.G. Beamer, E. Canalis, C.J. Rosen, Gender-specific changes in bone turnover and skeletal architecture in igfbp-2-null mice. Endocrinology 149(5), 2051–2061 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. J.V. Silha, S. Mishra, C.J. Rosen, W.G. Beamer, R.T. Turner, D.R. Powell, L.J. Murphy, Perturbations in bone formation and resorption in insulin-like growth factor binding protein-3 transgenic mice. J. Bone Miner. Res. 18(10), 1834–1841 (2003)

    Article  CAS  PubMed  Google Scholar 

  164. C. Richman, D.J. Baylink, K. Lang, C. Dony, S. Mohan, Recombinant human insulin-like growth factor-binding protein-5 stimulates bone formation parameters in vitro and in vivo. Endocrinology 140(10), 4699–4705 (1999)

    CAS  PubMed  Google Scholar 

  165. M.W. Hamrick, P.L. McNeil, S.L. Patterson, Role of muscle-derived growth factors in bone formation. J. Musculoskelet. Neuronal Interact. 10(1), 64–70 (2010)

    CAS  PubMed  PubMed Central  Google Scholar 

  166. M.B. Alzghoul, D. Gerrard, B.A. Watkins, K. Hannon, Ectopic expression of IGF-I and Shh by skeletal muscle inhibits disuse-mediated skeletal muscle atrophy and bone osteopenia in vivo. FASEB J. 18(1), 221–223 (2004)

    CAS  PubMed  Google Scholar 

  167. J. Banu, L. Wang, D.N. Kalu, Effects of increased muscle mass on bone in male mice overexpressing IGF-I in skeletal muscles. Calcif. Tissue Int. 73(2), 196–201 (2003)

    Article  CAS  PubMed  Google Scholar 

  168. S. Elis, Y. Wu, H.W. Courtland, H. Sun, C.J. Rosen, M.L. Adamo, S. Yakar, Increased serum IGF-1 levels protect the musculoskeletal system but are associated with elevated oxidative stress markers and increased mortality independent of tissue igf1 gene expression. Aging Cell 10(3), 547–550 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. C. Ehrnborg, K.H. Lange, R. Dall, J.S. Christiansen, P.A. Lundberg, R.C. Baxter, M.A. Boroujerdi, B.A. Bengtsson, M.L. Healey, C. Pentecost, S. Longobardi, R. Napoli, T. Rosen, G.H.S. Group, The growth hormone/insulin-like growth factor-I axis hormones and bone markers in elite athletes in response to a maximum exercise test. J. Clin. Endocrinol. Metab. 88, 394–401 (2003)

    Article  CAS  PubMed  Google Scholar 

  170. L.A. Milliken, S.B. Going, L.B. Houtkooper, H.G. Flint-Wagner, A. Figueroa, L.L. Metcalfe, R.M. Blew, S.C. Sharp, T.G. Lohman, Effects of exercise training on bone remodeling, insulin-like growth factors, and bone mineral density in postmenopausal women with and without hormone replacement therapy. Calcif. Tissue Int. 72(4), 478–484 (2003)

    Article  CAS  PubMed  Google Scholar 

  171. T. Soot, T. Jurimae, J. Jurimae, Relationships between bone mineral density, insulin-like growth factor-1 and sex hormones in young females with different physical activity. J. Sports Med. Phys. Fitness 46(2), 293–297 (2006)

    CAS  PubMed  Google Scholar 

  172. T. Pomerants, V. Tillmann, K. Karelson, J. Jurimae, T. Jurimae, Impact of acute exercise on bone turnover and growth hormone/insulin-like growth factor axis in boys. J. Sports Med. Phys. Fitness 48(2), 266–271 (2008)

    CAS  PubMed  Google Scholar 

  173. R. Gruodyte, J. Jurimae, M. Saar, T. Jurimae, The relationships among bone health, insulin-like growth factor-1 and sex hormones in adolescent female athletes. J. Bone Miner. Metab. 28(3), 306–313 (2010)

    Article  CAS  PubMed  Google Scholar 

  174. S. Perrini, L. Laviola, M.C. Carreira, A. Cignarelli, A. Natalicchio, F. Giorgino, The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis. J. Endocrinol. 205(3), 201–210 (2010)

    Article  CAS  PubMed  Google Scholar 

  175. Y. Tsuchiya, K. Sakuraba, E. Ochi, High force eccentric exercise enhances serum tartrate-resistant acid phosphatase-5b and osteocalcin. J. Musculoskelet. Neuronal Interact. 14(1), 50–57 (2014)

    CAS  PubMed  Google Scholar 

  176. D.A. Rubin, D.M. Castner, H. Pham, J. Ng, E. Adams, D.A. Judelson, Hormonal and metabolic responses to a resistance exercise protocol in lean children, obese children and lean adults. Pediatr. Exerc. Sci. 26(4), 444–454 (2014)

    Article  PubMed  Google Scholar 

  177. D.A. Rubin, H.N. Pham, E.S. Adams, A.R. Tutor, A.C. Hackney, J.W. Coburn, D.A. Judelson, Endocrine response to acute resistance exercise in obese versus lean physically active men. Eur. J. Appl. Physiol. 115(6), 1359–1366 (2015)

    Article  CAS  PubMed  Google Scholar 

  178. M.R. MohajeriTehrani, M. Tajvidi, S. Kahrizi, M. Hedayati, Does endurance training affect igf-1/igfbp-3 and insulin sensitivity in patients with type 2 diabetes? J. Sports Med. Phys. Fitness 55(9), 1004–1012 (2015)

    CAS  Google Scholar 

  179. B.C. Nindl, J.R. Pierce, Insulin-like growth factor I as a biomarker of health, fitness, and training status. Med. Sci. Sports Exerc. 42(1), 39–49 (2010)

    Article  CAS  PubMed  Google Scholar 

  180. B.C. Nindl, Insulin-like growth factor-I, physical activity, and control of cellular anabolism. Med. Sci. Sports Exerc. 42(1), 35–38 (2010)

    Article  CAS  PubMed  Google Scholar 

  181. E. Albrecht, F. Norheim, B. Thiede, T. Holen, T. Ohashi, L. Schering, S. Lee, J. Brenmoehl, S. Thomas, C.A. Drevon, H.P. Erickson, S. Maak, Irisin—a myth rather than an exercise-inducible myokine. Sci. Rep. 5, 8889 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. F. Sanchis-Gomar, R. Alis, G. Lippi, Circulating irisin detection: does it really work? Trends Endocrinol. Metab. 26(7), 335–336 (2015)

    Article  CAS  PubMed  Google Scholar 

  183. M.P. Jedrychowski, C.D. Wrann, J.A. Paulo, K.K. Gerber, J. Szpyt, M.M. Robinson, K.S. Nair, S.P. Gygi, B.M. Spiegelman, Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metab. 22(4), 734–740 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. P. Bostrom, J. Wu, M.P. Jedrychowski, A. Korde, L. Ye, J.C. Lo, K.A. Rasbach, E.A. Bostrom, J.H. Choi, J.Z. Long, S. Kajimura, M.C. Zingaretti, B.F. Vind, H. Tu, S. Cinti, K. Hojlund, S.P. Gygi, B.M. Spiegelman, A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481(7382), 463–468 (2012)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  185. J. Wu, P. Bostrom, L.M. Sparks, L. Ye, J.H. Choi, A.H. Giang, M. Khandekar, K.A. Virtanen, P. Nuutila, G. Schaart, K. Huang, H. Tu, W.D. van Marken Lichtenbelt, J. Hoeks, S. Enerback, P. Schrauwen, B.M. Spiegelman, Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150(2), 366–376 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. F. Sanchis-Gomar, C. Perez-Quilis, The p38-PGC-1alpha-irisin-betatrophin axis: exploring new pathways in insulin resistance. Adipocyte 3(1), 67–68 (2014)

    Article  PubMed  Google Scholar 

  187. S.S. Daskalopoulou, A.B. Cooke, Y.H. Gomez, A.F. Mutter, A. Filippaios, E.T. Mesfum, C.S. Mantzoros, Plasma irisin levels progressively increase in response to increasing exercise workloads in young, healthy, active subjects. Eur. J. Endocrinol. 171(3), 343–352 (2014)

    Article  CAS  PubMed  Google Scholar 

  188. R.R. Kraemer, P. Shockett, N.D. Webb, U. Shah, V.D. Castracane, A transient elevated irisin blood concentration in response to prolonged, moderate aerobic exercise in young men and women. Horm. Metab. Res. 46(2), 150–154 (2014)

    CAS  PubMed  Google Scholar 

  189. F. Norheim, T.M. Langleite, M. Hjorth, T. Holen, A. Kielland, H.K. Stadheim, H.L. Gulseth, K.I. Birkeland, J. Jensen, C.A. Drevon, The effects of acute and chronic exercise on PGC-1alpha, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 281(3), 739–749 (2014)

    Article  CAS  PubMed  Google Scholar 

  190. F. Sanchis-Gomar, R. Alis, H. Pareja-Galeano, E. Sola, V.M. Victor, M. Rocha, A. Hernandez-Mijares, M. Romagnoli, Circulating irisin levels are not correlated with BMI, age, and other biological parameters in obese and diabetic patients. Endocrine 46(3), 674–677 (2014)

    Article  CAS  PubMed  Google Scholar 

  191. A. Palermo, R. Strollo, E. Maddaloni, D. Tuccinardi, L. D’Onofrio, S.I. Briganti, G. Defeudis, M. De Pascalis, M.C. Lazzaro, G. Colleluori, S. Manfrini, P. Pozzilli, N. Napoli, Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity. Clin. Endocrinol. (Oxf.) 82(4), 615–619 (2015)

    Article  CAS  Google Scholar 

  192. A.D. Anastasilakis, S.A. Polyzos, P. Makras, A. Gkiomisi, I. Bisbinas, A. Katsarou, A. Filippaios, C.S. Mantzoros, Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months. Osteoporos. Int. 25(5), 1633–1642 (2014)

    Article  CAS  PubMed  Google Scholar 

  193. G. Colaianni, C. Cuscito, T. Mongelli, A. Oranger, G. Mori, G. Brunetti, S. Colucci, S. Cinti, M. Grano, Irisin enhances osteoblast differentiation in vitro. Int. J. Endocrinol. 2014, 902186 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  194. M. Mountjoy, J. Sundgot-Borgen, L. Burke, S. Carter, N. Constantini, C. Lebrun, N. Meyer, R. Sherman, K. Steffen, R. Budgett, A. Ljungqvist, The IOC consensus statement: beyond the Female Athlete Triad-Relative Energy Deficiency in Sport (RED-S). Br. J. Sports Med. 48(7), 491–497 (2014)

    Article  PubMed  Google Scholar 

  195. V. Singhal, E.A. Lawson, K.E. Ackerman, P.K. Fazeli, H. Clarke, H. Lee, K. Eddy, D.A. Marengi, N.P. Derrico, M.L. Bouxsein, M. Misra, Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates. PLoS ONE 9(6), e100218 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  196. T. Klangjareonchai, H. Nimitphong, S. Saetung, N. Bhirommuang, R. Samittarucksa, S. Chanprasertyothin, R. Sudatip, B. Ongphiphadhanakul, Circulating sclerostin and irisin are related and interact with gender to influence adiposity in adults with prediabetes. Int. J. Endocrinol. 2014, 261545 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  197. B. Garcia-Fontana, R. Reyes-Garcia, S. Morales-Santana, V. Avila-Rubio, A. Munoz-Garach, P. Rozas-Moreno, M. Munoz-Torres, Relationship between myostatin and irisin in type 2 diabetes mellitus: a compensatory mechanism to an unfavourable metabolic state? Endocrine (2015). doi:10.1007/s12020-015-0758-8

    PubMed  Google Scholar 

  198. G. Thomas, P. Moffatt, P. Salois, M.H. Gaumond, R. Gingras, E. Godin, D. Miao, D. Goltzman, C. Lanctot, Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype. J. Biol. Chem. 278(50), 50563–50571 (2003)

    Article  CAS  PubMed  Google Scholar 

  199. H. Nishizawa, M. Matsuda, Y. Yamada, K. Kawai, E. Suzuki, M. Makishima, T. Kitamura, I. Shimomura, Musclin, a novel skeletal muscle-derived secretory factor. J. Biol. Chem. 279(19), 19391–19395 (2004)

    Article  CAS  PubMed  Google Scholar 

  200. L.R. Potter, S. Abbey-Hosch, D.M. Dickey, Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr. Rev. 27(1), 47–72 (2006)

    Article  CAS  PubMed  Google Scholar 

  201. K.J. Motyl, L.R. McCabe, A.V. Schwartz, Bone and glucose metabolism: a two-way street. Arch. Biochem. Biophys. 503(1), 2–10 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. A. Yasui, H. Nishizawa, Y. Okuno, K. Morita, H. Kobayashi, K. Kawai, M. Matsuda, K. Kishida, S. Kihara, Y. Kamei, Y. Ogawa, T. Funahashi, I. Shimomura, Foxo1 represses expression of musclin, a skeletal muscle-derived secretory factor. Biochem. Biophys. Res. Commun. 364(2), 358–365 (2007)

    Article  CAS  PubMed  Google Scholar 

  203. R. Meeusen, Exercise, nutrition and the brain. Sports Med. 44(Suppl 1), S47–S56 (2014)

    Article  PubMed  Google Scholar 

  204. K. Iizuka, T. Machida, M. Hirafuji, Skeletal muscle is an endocrine organ. J. Pharmacol. Sci. 125(2), 125–131 (2014)

    Article  CAS  PubMed  Google Scholar 

  205. C. Camerino, M. Zayzafoon, M. Rymaszewski, J. Heiny, M. Rios, P.V. Hauschka, Central depletion of brain-derived neurotrophic factor in mice results in high bone mass and metabolic phenotype. Endocrinology 153(11), 5394–5405 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. K.L. Szuhany, M. Bugatti, M.W. Otto, A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J. Psychiatr. Res. 60, 56–64 (2015)

    Article  PubMed  Google Scholar 

  207. C. Phillips, M.A. Baktir, M. Srivatsan, A. Salehi, Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Front Cell Neurosci. 8, 170 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  208. M. Goekint, K. De Pauw, B. Roelands, R. Njemini, I. Bautmans, T. Mets, R. Meeusen, Strength training does not influence serum brain-derived neurotrophic factor. Eur. J. Appl. Physiol. 110(2), 285–293 (2010)

    Article  CAS  PubMed  Google Scholar 

  209. I. Bos, P. De Boever, L.I. Panis, R. Meeusen, Physical activity, air pollution and the brain. Sports Med. 44(11), 1505–1518 (2014)

    Article  PubMed  Google Scholar 

  210. O. Kilian, S. Hartmann, N. Dongowski, S. Karnati, E. Baumgart-Vogt, F.V. Hartel, T. Noll, R. Schnettler, K.S. Lips, BDNF and its TrkB receptor in human fracture healing. Ann. Anat. 196(5), 286–295 (2014)

    Article  PubMed  Google Scholar 

  211. T. Yamashiro, T. Fukunaga, K. Yamashita, N. Kobashi, T. Takano-Yamamoto, Gene and protein expression of brain-derived neurotrophic factor and TrkB in bone and cartilage. Bone 28(4), 404–409 (2001)

    Article  CAS  PubMed  Google Scholar 

  212. J.Z. Ilich, O.J. Kelly, J.E. Inglis, L.B. Panton, G. Duque, M.J. Ormsbee, Interrelationship among muscle, fat, and bone: connecting the dots on cellular, hormonal, and whole body levels. Ageing Res. Rev. 15, 51–60 (2014)

    Article  CAS  PubMed  Google Scholar 

  213. F. Sanchis-Gomar, R. Alis, E. Rampinini, A. Bosio, D. Ferioli, A. La Torre, J. Xu, V. Sansoni, S. Perego, M. Romagnoli, G. Lombardi, Adropin and apelin fluctuations throughout a season in professional soccer players: are they related with performance? Peptides 70, 32–36 (2015)

    Article  CAS  PubMed  Google Scholar 

  214. S. Migliaccio, E.A. Greco, R. Fornari, L.M. Donini, A. Lenzi, Is obesity in women protective against osteoporosis? Diabetes Metab. Syndr. Obes. 4, 273–282 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  215. J.J. Cao, Effects of obesity on bone metabolism. J. Orthop. Surg. Res. 6, 30 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  216. Y. Kim, O.J. Kelly, J.Z. Ilich, Synergism of alpha-linolenic acid, conjugated linoleic acid and calcium in decreasing adipocyte and increasing osteoblast cell growth. Lipids 48(8), 787–802 (2013)

    Article  CAS  PubMed  Google Scholar 

  217. A. Pratesi, F. Tarantini, M. Di Bari, Skeletal muscle: an endocrine organ. Clin. Cases Miner. Bone Metab. 10(1), 11–14 (2013)

    PubMed  PubMed Central  Google Scholar 

  218. I. Beyer, T. Mets, I. Bautmans, Chronic low-grade inflammation and age-related sarcopenia. Curr. Opin. Clin. Nutr. Metab. Care 15(1), 12–22 (2012)

    Article  CAS  PubMed  Google Scholar 

  219. B. Cannon, J. Nedergaard, Brown adipose tissue: function and physiological significance. Physiol. Rev. 84(1), 277–359 (2004)

    Article  CAS  PubMed  Google Scholar 

  220. S. Boeuf, M. Klingenspor, N.L. Van Hal, T. Schneider, J. Keijer, S. Klaus, Differential gene expression in white and brown preadipocytes. Physiol. Genomics 7(1), 15–25 (2001)

    Article  CAS  PubMed  Google Scholar 

  221. J. Kopecky, M. Baudysova, F. Zanotti, D. Janikova, S. Pavelka, J. Houstek, Synthesis of mitochondrial uncoupling protein in brown adipocytes differentiated in cell culture. J. Biol. Chem. 265(36), 22204–22209 (1990)

    CAS  PubMed  Google Scholar 

  222. P. Puigserver, B.M. Spiegelman, Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr. Rev. 24(1), 78–90 (2003)

    Article  CAS  PubMed  Google Scholar 

  223. S. Gesta, Y.H. Tseng, C.R. Kahn, Developmental origin of fat: tracking obesity to its source. Cell 131(2), 242–256 (2007)

    Article  CAS  PubMed  Google Scholar 

  224. H. Wallberg-Henriksson, J.R. Zierath, Metabolism. Exercise remodels subcutaneous fat tissue and improves metabolism. Nat. Rev. Endocrinol. 11(4), 198–200 (2015)

    Article  CAS  PubMed  Google Scholar 

  225. E.D. Rosen, B.M. Spiegelman, What we talk about when we talk about fat. Cell 156(1–2), 20–44 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. T.T. Tran, Y. Yamamoto, S. Gesta, C.R. Kahn, Beneficial effects of subcutaneous fat transplantation on metabolism. Cell Metab. 7(5), 410–420 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. K.I. Stanford, R.J. Middelbeek, K.L. Townsend, M.Y. Lee, H. Takahashi, K. So, K.M. Hitchcox, K.R. Markan, K. Hellbach, M.F. Hirshman, Y.H. Tseng, L.J. Goodyear, A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis. Diabetes 64(6), 2002–2014 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. M. Bosma, Lipid homeostasis in exercise. Drug Discov. Today 19(7), 1019–1023 (2014)

    Article  CAS  PubMed  Google Scholar 

  229. H. Wang, J. Ye, Regulation of energy balance by inflammation: common theme in physiology and pathology. Rev. Endocr. Metab. Disord. 16(1), 47–54 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. J. Himms-Hagen, Exercise in a pill: feasibility of energy expenditure targets. Curr. Drug Targets CNS Neurol. Disord. 3(5), 389–409 (2004)

    Article  CAS  PubMed  Google Scholar 

  231. E. Wolsk, H. Mygind, T.S. Grondahl, B.K. Pedersen, G. van Hall, IL-6 selectively stimulates fat metabolism in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 299(5), E832–E840 (2010)

    Article  CAS  PubMed  Google Scholar 

  232. M. Petruzzelli, M. Schweiger, R. Schreiber, R. Campos-Olivas, M. Tsoli, J. Allen, M. Swarbrick, S. Rose-John, M. Rincon, G. Robertson, R. Zechner, E.F. Wagner, A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab. 20(3), 433–447 (2014)

    Article  CAS  PubMed  Google Scholar 

  233. R. Armamento-Villareal, C. Sadler, N. Napoli, K. Shah, S. Chode, D.R. Sinacore, C. Qualls, D.T. Villareal, Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training. J. Bone Miner. Res. 27(5), 1215–1221 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. J.R. Berggren, M.W. Hulver, J.A. Houmard, Fat as an endocrine organ: influence of exercise. J. Appl. Physiol. 99(2), 757–764 (2005)

    Article  CAS  PubMed  Google Scholar 

  235. E. Biver, C. Salliot, C. Combescure, L. Gossec, P. Hardouin, I. Legroux-Gerot, B. Cortet, Influence of adipokines and ghrelin on bone mineral density and fracture risk: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 96(9), 2703–2713 (2011)

    Article  CAS  PubMed  Google Scholar 

  236. G. Duque, B.R. Troen, Understanding the mechanisms of senile osteoporosis: new facts for a major geriatric syndrome. J. Am. Geriatr. Soc. 56(5), 935–941 (2008)

    Article  PubMed  Google Scholar 

  237. K. Gunaratnam, C. Vidal, J.M. Gimble, G. Duque, Mechanisms of palmitate-induced lipotoxicity in human osteoblasts. Endocrinology 155(1), 108–116 (2014)

    Article  PubMed  CAS  Google Scholar 

  238. M. Zaidi, C. Buettner, L. Sun, J. Iqbal, Minireview: the link between fat and bone: does mass beget mass? Endocrinology 153(5), 2070–2075 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. J. Upadhyay, O.M. Farr, C.S. Mantzoros, The role of leptin in regulating bone metabolism. Metabolism 64(1), 105–113 (2015)

    Article  CAS  PubMed  Google Scholar 

  240. J.F. Caro, J.W. Kolaczynski, M.R. Nyce, J.P. Ohannesian, I. Opentanova, W.H. Goldman, R.B. Lynn, P.L. Zhang, M.K. Sinha, R.V. Considine, Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 348(9021), 159–161 (1996)

    Article  CAS  PubMed  Google Scholar 

  241. C.T. Montague, I.S. Farooqi, J.P. Whitehead, M.A. Soos, H. Rau, N.J. Wareham, C.P. Sewter, J.E. Digby, S.N. Mohammed, J.A. Hurst, C.H. Cheetham, A.R. Earley, A.H. Barnett, J.B. Prins, S. O’Rahilly, Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387(6636), 903–908 (1997)

    Article  CAS  PubMed  Google Scholar 

  242. R.V. Considine, E.L. Considine, C.J. Williams, M.R. Nyce, S.A. Magosin, T.L. Bauer, E.L. Rosato, J. Colberg, J.F. Caro, Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J. Clin. Invest. 95(6), 2986–2988 (1995)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. S.G. Hassink, D.V. Sheslow, E. de Lancey, I. Opentanova, R.V. Considine, J.F. Caro, Serum leptin in children with obesity: relationship to gender and development. Pediatrics 98(2 Pt 1), 201–203 (1996)

    CAS  PubMed  Google Scholar 

  244. S. Takeda, F. Elefteriou, R. Levasseur, X. Liu, L. Zhao, K.L. Parker, D. Armstrong, P. Ducy, G. Karsenty, Leptin regulates bone formation via the sympathetic nervous system. Cell 111(3), 305–317 (2002)

    Article  CAS  PubMed  Google Scholar 

  245. E. Sienkiewicz, F. Magkos, K.N. Aronis, M. Brinkoetter, J.P. Chamberland, S. Chou, K.M. Arampatzi, C. Gao, A. Koniaris, C.S. Mantzoros, Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women. Metabolism 60(9), 1211–1221 (2011)

    Article  CAS  PubMed  Google Scholar 

  246. Y.S. Kim, J.S. Nam, D.W. Yeo, K.R. Kim, S.H. Suh, C.W. Ahn, The effects of aerobic exercise training on serum osteocalcin, adipocytokines and insulin resistance on obese young males. Clin. Endocrinol. (Oxf.) 82(5), 686–694 (2015)

    Article  CAS  Google Scholar 

  247. C. Yang, J. Chen, F. Wu, J. Li, P. Liang, H. Zhang, H. Wang, Y. Li, Y. Wan, L. Qin, K.S. Liang, Z. Dai, Y. Li, Effects of 60-day head-down bed rest on osteocalcin, glycolipid metabolism and their association with or without resistance training. Clin. Endocrinol. (Oxf.) 81(5), 671–678 (2014)

    Article  CAS  Google Scholar 

  248. R.M. Campos, M.T. de Mello, L. Tock, P.L. Silva, D.C. Masquio, A. de Piano, P.L. Sanches, J. Carnier, F.C. Corgosinho, D. Foschini, S. Tufik, A.R. Damaso, Aerobic plus resistance training improves bone metabolism and inflammation in adolescents who are obese. J. Strength Cond. Res. 28(3), 758–766 (2014)

    Article  PubMed  Google Scholar 

  249. J.S. Lim, G.C. Jang, K.R. Moon, E.Y. Kim, Combined aerobic and resistance exercise is effective for achieving weight loss and reducing cardiovascular risk factors without deteriorating bone health in obese young adults. Ann. Pediatr. Endocrinol. Metab. 18(1), 26–31 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  250. K. Shah, R. Armamento-Villareal, N. Parimi, S. Chode, D.R. Sinacore, T.N. Hilton, N. Napoli, C. Qualls, D.T. Villareal, Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip bone mineral density induced by weight loss despite decline in bone-active hormones. J. Bone Miner. Res. 26(12), 2851–2859 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. V.D. Sherk, D.W. Barry, K.L. Villalon, K.C. Hansen, P. Wolfe, W.M. Kohrt, Bone loss over 1 year of training and competition in female cyclists. Clin. J. Sport Med. 24, 331–336 (2013)

    Article  Google Scholar 

  252. M.J. Santos, J.E. Fonseca, Metabolic syndrome, inflammation and atherosclerosis—the role of adipokines in health and in systemic inflammatory rheumatic diseases. Acta Reumatol. Port 34(4), 590–598 (2009)

    PubMed  Google Scholar 

  253. M. Ruscica, L. Steffani, P. Magni, Adiponectin interactions in bone and cartilage biology and disease. Vitam. Horm. 90, 321–339 (2012)

    Article  CAS  PubMed  Google Scholar 

  254. N. Sucunza, M.J. Barahona, E. Resmini, J.M. Fernandez-Real, W. Ricart, J. Farrerons, J. Rodriguez Espinosa, A.M. Marin, T. Puig, S.M. Webb, A link between bone mineral density and serum adiponectin and visfatin levels in acromegaly. J. Clin. Endocrinol. Metab. 94(10), 3889–3896 (2009)

    Article  CAS  PubMed  Google Scholar 

  255. A. Lubkowska, A. Dobek, J. Mieszkowski, W. Garczynski, D. Chlubek, Adiponectin as a biomarker of osteoporosis in postmenopausal women: controversies. Dis. Markers 2014, 975178 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  256. H.S. Berner, S.P. Lyngstadaas, A. Spahr, M. Monjo, L. Thommesen, C.A. Drevon, U. Syversen, J.E. Reseland, Adiponectin and its receptors are expressed in bone-forming cells. Bone 35(4), 842–849 (2004)

    Article  CAS  PubMed  Google Scholar 

  257. Y. Shinoda, M. Yamaguchi, N. Ogata, T. Akune, N. Kubota, T. Yamauchi, Y. Terauchi, T. Kadowaki, Y. Takeuchi, S. Fukumoto, T. Ikeda, K. Hoshi, U.I. Chung, K. Nakamura, H. Kawaguchi, Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J. Cell. Biochem. 99(1), 196–208 (2006)

    Article  CAS  PubMed  Google Scholar 

  258. H. Sadie-Van Gijsen, N.J. Crowther, F.S. Hough, W.F. Ferris, The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity. Cell. Mol. Life Sci. 70(13), 2331–2349 (2013)

    Article  CAS  PubMed  Google Scholar 

  259. Y. Zhang, P. Zhou, J.W. Kimondo, Adiponectin and osteocalcin: relation to insulin sensitivity. Biochem. Cell Biol. 90(5), 613–620 (2012)

    Article  CAS  PubMed  Google Scholar 

  260. S. Balducci, S. Zanuso, A. Nicolucci, F. Fernando, S. Cavallo, P. Cardelli, S. Fallucca, E. Alessi, C. Letizia, A. Jimenez, F. Fallucca, G. Pugliese, Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nutr. Metab. Cardiovasc. Dis. 20(8), 608–617 (2010)

    Article  CAS  PubMed  Google Scholar 

  261. S. Lim, S.H. Choi, I.K. Jeong, J.H. Kim, M.K. Moon, K.S. Park, H.K. Lee, Y.B. Kim, H.C. Jang, Insulin-sensitizing effects of exercise on adiponectin and retinol-binding protein-4 concentrations in young and middle-aged women. J. Clin. Endocrinol. Metab. 93(6), 2263–2268 (2008)

    Article  CAS  PubMed  Google Scholar 

  262. Y.H. Ku, K.A. Han, H. Ahn, H. Kwon, B.K. Koo, H.C. Kim, K.W. Min, Resistance exercise did not alter intramuscular adipose tissue but reduced retinol-binding protein-4 concentration in individuals with type 2 diabetes mellitus. J. Int. Med. Res. 38(3), 782–791 (2010)

    Article  CAS  PubMed  Google Scholar 

  263. K.A. Simpson, M.A. Singh, Effects of exercise on adiponectin: a systematic review. Obesity (Silver Spring) 16(2), 241–256 (2008)

    Article  CAS  Google Scholar 

  264. A.L. Parm, J. Jurimae, M. Saar, K. Parna, V. Tillmann, K. Maasalu, I. Neissaar, T. Jurimae, Plasma adipocytokine and ghrelin levels in relation to bone mineral density in prepubertal rhythmic gymnasts. J. Bone Miner. Metab. 29(6), 717–724 (2011)

    Article  CAS  PubMed  Google Scholar 

  265. J. Jurimae, T. Kums, T. Jurimae, Adipocytokine and ghrelin levels in relation to bone mineral density in physically active older women: longitudinal associations. Eur. J. Endocrinol. 160(3), 381–385 (2009)

    Article  CAS  PubMed  Google Scholar 

  266. J. Jurimae, R. Ramson, J. Maestu, T. Jurimae, P.J. Arciero, W.A. Braun, L.M. LeMura, S.P. Von Duvillard, Interactions between adipose, bone, and muscle tissue markers during acute negative energy balance in male rowers. J. Sports Med. Phys. Fitness 51(2), 347–354 (2011)

    CAS  PubMed  Google Scholar 

  267. A. Fukuhara, M. Matsuda, M. Nishizawa, K. Segawa, M. Tanaka, K. Kishimoto, Y. Matsuki, M. Murakami, T. Ichisaka, H. Murakami, E. Watanabe, T. Takagi, M. Akiyoshi, T. Ohtsubo, S. Kihara, S. Yamashita, M. Makishima, T. Funahashi, S. Yamanaka, R. Hiramatsu, Y. Matsuzawa, I. Shimomura, Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307(5708), 426–430 (2005)

    Article  CAS  PubMed  Google Scholar 

  268. G. Lombardi, G. Banfi, Effects of sample matrix and storage conditions on full-length visfatin measurement in blood. Clin. Chim. Acta 440, 140–142 (2015)

    Article  CAS  PubMed  Google Scholar 

  269. G. Sommer, A. Garten, S. Petzold, A.G. Beck-Sickinger, M. Bluher, M. Stumvoll, M. Fasshauer, Visfatin/PBEF/Nampt: structure, regulation and potential function of a novel adipokine. Clin. Sci. (Lond.) 115(1), 13–23 (2008)

    Article  CAS  Google Scholar 

  270. L. Thommesen, A.K. Stunes, M. Monjo, K. Grosvik, M.V. Tamburstuen, E. Kjobli, S.P. Lyngstadaas, J.E. Reseland, U. Syversen, Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism. J. Cell. Biochem. 99(3), 824–834 (2006)

    Article  CAS  PubMed  Google Scholar 

  271. H. Xie, S.Y. Tang, X.H. Luo, J. Huang, R.R. Cui, L.Q. Yuan, H.D. Zhou, X.P. Wu, E.Y. Liao, Insulin-like effects of visfatin on human osteoblasts. Calcif. Tissue Int. 80(3), 201–210 (2007)

    Article  CAS  PubMed  Google Scholar 

  272. A.R. Moschen, S. Geiger, R. Gerner, H. Tilg, Pre-B cell colony enhancing factor/NAMPT/visfatin and its role in inflammation-related bone disease. Mutat. Res. 690(1–2), 95–101 (2010)

    Article  CAS  PubMed  Google Scholar 

  273. Y. Li, X. He, Y. Li, J. He, B. Anderstam, G. Andersson, U. Lindgren, Nicotinamide phosphoribosyltransferase (Nampt) affects the lineage fate determination of mesenchymal stem cells: a possible cause for reduced osteogenesis and increased adipogenesis in older individuals. J. Bone Miner. Res. 26(11), 2656–2664 (2011)

    Article  CAS  PubMed  Google Scholar 

  274. S.R. Costford, S. Bajpeyi, M. Pasarica, D.C. Albarado, S.C. Thomas, H. Xie, T.S. Church, S.A. Jubrias, K.E. Conley, S.R. Smith, Skeletal muscle NAMPT is induced by exercise in humans. Am. J. Physiol. Endocrinol. Metab. 298(1), E117–E126 (2010)

    Article  CAS  PubMed  Google Scholar 

  275. A. Ghanbari-Niaki, M. Saghebjoo, R. Soltani, J.P. Kirwan, Plasma visfatin is increased after high-intensity exercise. Ann. Nutr. Metab. 57(1), 3–8 (2010)

    Article  CAS  PubMed  Google Scholar 

  276. D. Friebe, M. Neef, J. Kratzsch, S. Erbs, K. Dittrich, A. Garten, S. Petzold-Quinque, S. Bluher, T. Reinehr, M. Stumvoll, M. Bluher, W. Kiess, A. Korner, Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans. Diabetologia 54(5), 1200–1211 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  277. I. Brema, M. Hatunic, F. Finucane, N. Burns, J.J. Nolan, D. Haider, M. Wolzt, B. Ludvik, Plasma visfatin is reduced after aerobic exercise in early onset type 2 diabetes mellitus. Diabetes Obes. Metab. 10(7), 600–602 (2008)

    Article  CAS  PubMed  Google Scholar 

  278. M.L. Jorge, V.N. de Oliveira, N.M. Resende, L.F. Paraiso, A. Calixto, A.L. Diniz, E.S. Resende, E.R. Ropelle, J.B. Carvalheira, F.S. Espindola, P.T. Jorge, B. Geloneze, The effects of aerobic, resistance, and combined exercise on metabolic control, inflammatory markers, adipocytokines, and muscle insulin signaling in patients with type 2 diabetes mellitus. Metabolism 60(9), 1244–1252 (2011)

    Article  CAS  PubMed  Google Scholar 

  279. G. Banfi, G. Lombardi, A. Colombini, G. Melegati, Whole-body cryotherapy in athletes. Sports Med. 40(6), 509–517 (2010)

    Article  PubMed  Google Scholar 

  280. A. Lubkowska, W. Dudzinska, I. Bryczkowska, B. Dolegowska, Body composition, lipid profile, adipokine concentration, and antioxidant capacity changes during interventions to treat overweight with exercise programme and whole-body cryostimulation. Oxid. Med. Cell Longev. 2015, 803197 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  281. S. Bo, G. Ciccone, I. Baldi, R. Gambino, C. Mandrile, M. Durazzo, L. Gentile, M. Cassader, P. Cavallo-Perin, G. Pagano, Plasma visfatin concentrations after a lifestyle intervention were directly associated with inflammatory markers. Nutr. Metab. Cardiovasc. Dis. 19(6), 423–430 (2009)

    Article  CAS  PubMed  Google Scholar 

  282. S. Aggeloussi, A.A. Theodorou, V. Paschalis, M.G. Nikolaidis, I.G. Fatouros, E.O. Owolabi, D. Kouretas, Y. Koutedakis, A.Z. Jamurtas, Adipocytokine levels in children: effects of fatness and training. Pediatr. Exerc. Sci. 24(3), 461–471 (2012)

    Article  PubMed  Google Scholar 

  283. J.P. Walhin, J.D. Richardson, J.A. Betts, D. Thompson, Exercise counteracts the effects of short-term overfeeding and reduced physical activity independent of energy imbalance in healthy young men. J. Physiol. 591(Pt 24), 6231–6243 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  284. A. Petelin, M. Bizjak, M. Cernelic-Bizjak, M. Jurdana, T. Jakus, Z. Jenko-Praznikar, Low-grade inflammation in overweight and obese adults is affected by weight loss program. J. Endocrinol. Invest. 37(8), 745–755 (2014)

    Article  CAS  PubMed  Google Scholar 

  285. J. Jurimae, R. Ramson, J. Maestu, P. Purge, T. Jurimae, P.J. Arciero, S.P. von Duvillard, Plasma visfatin and ghrelin response to prolonged sculling in competitive male rowers. Med. Sci. Sports Exerc. 41(1), 137–143 (2009)

    Article  CAS  PubMed  Google Scholar 

  286. J.M. Haus, T.P. Solomon, C.M. Marchetti, V.B. O’Leary, L.M. Brooks, F. Gonzalez, J.P. Kirwan, Decreased visfatin after exercise training correlates with improved glucose tolerance. Med. Sci. Sports Exerc. 41(6), 1255–1260 (2009)

    Article  CAS  PubMed  Google Scholar 

  287. E. Sliwicka, A. Nowak, W. Zep, P. Leszczynski, L. Pilaczynska-Szczesniak, Bone mass and bone metabolic indices in male master rowers. J. Bone Miner. Metab. 33(5), 540–546 (2015)

    Article  CAS  PubMed  Google Scholar 

  288. H. Zhang, H. Xie, Q. Zhao, G.Q. Xie, X.P. Wu, E.Y. Liao, X.H. Luo, Relationships between serum adiponectin, apelin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in post-menopausal Chinese women. J. Endocrinol. Invest. 33(10), 707–711 (2010)

    Article  CAS  PubMed  Google Scholar 

  289. X.D. Peng, H. Xie, Q. Zhao, X.P. Wu, Z.Q. Sun, E.Y. Liao, Relationships between serum adiponectin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in Chinese men. Clin. Chim. Acta 387(1–2), 31–35 (2008)

    Article  CAS  PubMed  Google Scholar 

  290. M. Tohidi, S. Akbarzadeh, B. Larijani, M. Kalantarhormozi, A. Ostovar, M. Assadi, K. Vahdat, M. Farrokhnia, Z. Sanjdideh, R. Amirinejad, I. Nabipour, Omentin-1, visfatin and adiponectin levels in relation to bone mineral density in Iranian postmenopausal women. Bone 51(5), 876–881 (2012)

    Article  CAS  PubMed  Google Scholar 

  291. R. Gruodyte, J. Jurimae, A. Cicchella, C. Stefanelli, C. Passariello, T. Jurimae, Adipocytokines and bone mineral density in adolescent female athletes. Acta Paediatr. 99(12), 1879–1884 (2010)

    Article  CAS  PubMed  Google Scholar 

  292. G. Iacobellis, M. Iorio, N. Napoli, D. Cotesta, L. Zinnamosca, C. Marinelli, L. Petramala, S. Minisola, E. D’Erasmo, C. Letizia, Relation of adiponectin, visfatin and bone mineral density in patients with metabolic syndrome. J. Endocrinol. Invest. 34(1), e12–e15 (2011)

    Article  CAS  PubMed  Google Scholar 

  293. P. Codoner-Franch, E. Alonso-Iglesias, Resistin: insulin resistance to malignancy. Clin. Chim. Acta 438, 46–54 (2015)

    Article  CAS  PubMed  Google Scholar 

  294. K.W. Oh, W.Y. Lee, E.J. Rhee, K.H. Baek, K.H. Yoon, M.I. Kang, E.J. Yun, C.Y. Park, S.H. Ihm, M.G. Choi, H.J. Yoo, S.W. Park, The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men. Clin. Endocrinol. (Oxf.) 63(2), 131–138 (2005)

    Article  CAS  Google Scholar 

  295. W. Pluskiewicz, P. Adamczyk, B. Marek, A. Czekajlo, B. Drozdzowska, D. Kajdaniuk, B. Kos-Kudla, W. Grzeszczak, Adiponectin and resistin in relationship with skeletal status in women from the RAC-OST-POL study. Endokrynol. Pol. 63(6), 427–431 (2012)

    CAS  PubMed  Google Scholar 

  296. J. Mohiti-Ardekani, H. Soleymani-Salehabadi, M.B. Owlia, A. Mohiti, Relationships between serum adipocyte hormones (adiponectin, leptin, resistin), bone mineral density and bone metabolic markers in osteoporosis patients. J. Bone Miner. Metab. 32(4), 400–404 (2014)

    Article  CAS  PubMed  Google Scholar 

  297. M.R. Sowers, R.P. Wildman, P. Mancuso, A.D. Eyvazzadeh, C.A. Karvonen-Gutierrez, E. Rillamas-Sun, M.L. Jannausch, Change in adipocytokines and ghrelin with menopause. Maturitas 59(2), 149–157 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  298. A. Fisher, E. Southcott, R. Li, W. Srikusalanukul, M. Davis, P. Smith, Serum resistin in older patients with hip fracture: relationship with comorbidity and biochemical determinants of bone metabolism. Cytokine 56(2), 157–166 (2011)

    Article  CAS  PubMed  Google Scholar 

  299. M.S. Albadah, H. Dekhil, S.A. Shaik, M.A. Alsaif, M. Shogair, S. Nawaz, A.A. Alfadda, Effect of weight loss on serum osteocalcin and its association with serum adipokines. Int. J. Endocrinol. 2015, 508532 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  300. E. Hopps, B. Canino, G. Caimi, Effects of exercise on inflammation markers in type 2 diabetic subjects. Acta Diabetol. 48(3), 183–189 (2011)

    Article  CAS  PubMed  Google Scholar 

  301. A. Jamurtas, A. Stavropoulos-Kalinoglou, S. Koutsias, Y. Koutedakis, I. Fatouros, Adiponectin, resistin and visfatin in childhood obesity and exercise. Pediatr. Exerc. Sci. (2015). doi:10.1123/pes.2014-0072

    PubMed  Google Scholar 

  302. E. Joy, M.J. De Souza, A. Nattiv, M. Misra, N.I. Williams, R.J. Mallinson, J.C. Gibbs, M. Olmsted, M. Goolsby, G. Matheson, M. Barrack, L. Burke, B. Drinkwater, C. Lebrun, A.B. Loucks, M. Mountjoy, J. Nichols, J.S. Borgen, 2014 female athlete triad coalition consensus statement on treatment and return to play of the female athlete triad. Curr. Sports Med. Rep. 13(4), 219–232 (2014)

    Article  PubMed  Google Scholar 

  303. J. Sundgot-Borgen, N.L. Meyer, T.G. Lohman, T.R. Ackland, R.J. Maughan, A.D. Stewart, W. Muller, How to minimise the health risks to athletes who compete in weight-sensitive sports review and position statement on behalf of the Ad Hoc Research Working Group on Body Composition, Health and Performance, under the auspices of the IOC Medical Commission. Br. J. Sports Med. 47(16), 1012–1022 (2013)

    Article  PubMed  Google Scholar 

  304. E. Stice, K. South, H. Shaw, Future directions in etiologic, prevention, and treatment research for eating disorders. J. Clin. Child Adolesc. Psychol. 41(6), 845–855 (2012)

    Article  PubMed  Google Scholar 

  305. J. Sundgot-Borgen, M.K. Torstveit, Aspects of disordered eating continuum in elite high-intensity sports. Scand. J. Med. Sci. Sports 20(Suppl 2), 112–121 (2010)

    Article  PubMed  Google Scholar 

  306. G.N. Wade, J.E. Jones, Neuroendocrinology of nutritional infertility. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287(6), R1277–R1296 (2004)

    Article  CAS  PubMed  Google Scholar 

  307. A. Nattiv, A.B. Loucks, M.M. Manore, C.F. Sanborn, J. Sundgot-Borgen, M.P. Warren, M. American, College of Sports, American College of Sports Medicine position stand. The female athlete triad. Med. Sci. Sports Exerc. 39(10), 1867–1882 (2007)

    Article  PubMed  Google Scholar 

  308. J.L. Areta, L.M. Burke, M.L. Ross, D.M. Camera, D.W. West, E.M. Broad, N.A. Jeacocke, D.R. Moore, T. Stellingwerff, S.M. Phillips, J.A. Hawley, V.G. Coffey, Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis. J. Physiol. 591(Pt 9), 2319–2331 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  309. D. Li, C.L. Hitchcock, S.I. Barr, T. Yu, J.C. Prior, Negative spinal bone mineral density changes and subclinical ovulatory disturbances—prospective data in healthy premenopausal women with regular menstrual cycles. Epidemiol. Rev. 36, 137–147 (2014)

    Article  CAS  PubMed  Google Scholar 

  310. K.E. Ackerman, M. Putman, G. Guereca, A.P. Taylor, L. Pierce, D.B. Herzog, A. Klibanski, M. Bouxsein, M. Misra, Cortical microstructure and estimated bone strength in young amenorrheic athletes, eumenorrheic athletes and non-athletes. Bone 51(4), 680–687 (2012)

    Article  PubMed  PubMed Central  Google Scholar 

  311. I. Lambrinoudaki, D. Papadimitriou, Pathophysiology of bone loss in the female athlete. Ann. N. Y. Acad. Sci. 1205, 45–50 (2010)

    Article  CAS  PubMed  Google Scholar 

  312. A.D. Keen, B.L. Drinkwater, Irreversible bone loss in former amenorrheic athletes. Osteoporos. Int. 7(4), 311–315 (1997)

    Article  CAS  PubMed  Google Scholar 

  313. M.T. Barrack, M.D. Van Loan, M.J. Rauh, J.F. Nichols, Physiologic and behavioral indicators of energy deficiency in female adolescent runners with elevated bone turnover. Am. J. Clin. Nutr. 92(3), 652–659 (2010)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work has been funded by the Italian Ministry of Health.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Giovanni Lombardi.

Ethics declarations

Conflicts of interest

The authors declare no conflicts of interest concerning this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lombardi, G., Sanchis-Gomar, F., Perego, S. et al. Implications of exercise-induced adipo-myokines in bone metabolism. Endocrine 54, 284–305 (2016). https://doi.org/10.1007/s12020-015-0834-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-015-0834-0

Keywords

Navigation