Skip to main content
SpringerLink
Log in

Effects of Diet-Induced Obesity and Voluntary Wheel Running on Bone Properties in Young Male C57BL/6J Mice

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Both physical activity and body mass affect bone properties. In this study we examined how diet-induced obesity combined with voluntary physical activity affects bone properties. Forty 7-week-old male C57BL/6J mice were assigned to four groups evenly: control diet (C), control diet + running (CR), high-fat diet (HF, 60% energy from fat), and high-fat diet + running (HFR). After 21-week intervention, all mice were killed and the left femur was dissected for pQCT and mechanical measurements. Body mass increased 80% in HF and 62% in HFR, with increased epididymal fat pad weight and impaired insulin sensitivity. Except for total and trabecular volumetric bone mineral density (BMD), bone traits correlated positively with body mass, fat pad, leptin, and osteoprotegerin. Obesity induced by a high-fat diet resulted in increased femoral bone cross-sectional area, mineral content (BMC), polar moment of inertia, and mechanical parameters. Of the mice accessing the running wheel, those fed the control diet had thinner cortex and less total metaphyseal BMC and BMD, with enlarged metaphyseal marrow cavity, whereas mice fed the high-fat diet had significantly higher trabecular BMD and smaller marrow cavity. However, the runners had a weaker femoral neck as indicated by decreased maximum flexure load. These results suggest that voluntary running exercise affects bone properties in a site-specific manner and that there is a complex interaction between physical activity and obesity. Thus, both diet and exercise should be considered when optimizing the effects on body composition and bone, even though the underlying mechanisms remain partly unknown.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Rosen CJ, Bouxsein ML (2006) Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol 2:35–43

    Article  PubMed  CAS  Google Scholar 

  2. Gimble JM, Zvonic S, Floyd ZE, Kassem M, Nuttall ME (2006) Playing with bone and fat. J Cell Biochem 98:251–266

    Article  PubMed  CAS  Google Scholar 

  3. Hausman GJ, Hausman DB (2006) Search for the preadipocyte progenitor cell. J Clin Investig 116:3103–3106

    Article  PubMed  CAS  Google Scholar 

  4. Jebb SA, Moore MS (1999) Contribution of a sedentary lifestyle and inactivity to the etiology of overweight and obesity: current evidence and research issues. Med Sci Sports Exerc 31:S534–S541

    Article  PubMed  CAS  Google Scholar 

  5. Resnick HE, Carter EA, Aloia M, Phillips B (2006) Cross-sectional relationship of reported fatigue to obesity, diet, and physical activity: results from the Third National Health and Nutrition Examination Survey. J Clin Sleep Med 2:163–169

    PubMed  Google Scholar 

  6. Williams TD, Chambers JB, Roberts LM, Henderson RP, Overton JM (2003) Diet-induced obesity and cardiovascular regulation in C57BL/6J mice. Clin Exp Pharmacol Physiol 30:769–778

    Article  PubMed  CAS  Google Scholar 

  7. Shuldiner AR (2008) Obesity genes and gene–environment–behavior interactions: recommendations for a way forward. Obesity (Silver Spring) 16:S79–S81

    Article  CAS  Google Scholar 

  8. Gomez-Ambrosi J, Rodriguez A, Catalan V, Fruhbeck G (2008) The bone–adipose axis in obesity and weight loss. Obes Surg 18:1134–1143

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  10. Pollock NK, Laing EM, Baile CA, Hamrick MW, Hall DB, Lewis RD (2007) Is adiposity advantageous for bone strength? A peripheral quantitative computed tomography study in late adolescent females. Am J Clin Nutr 86:1530–1538

    PubMed  CAS  Google Scholar 

  11. Reid IR (2008) Relationships between fat and bone. Osteoporos Int 19:595–606

    Article  PubMed  CAS  Google Scholar 

  12. Janz KF, Gilmore JM, Levy SM, Letuchy EM, Burns TL, Beck TJ (2007) Physical activity and femoral neck bone strength during childhood: the Iowa Bone Development Study. Bone 41:216–222

    Article  PubMed  Google Scholar 

  13. Sone T, Imai Y, Joo YI, Onodera S, Tomomitsu T, Fukunaga M (2006) Side-to-side differences in cortical bone mineral density of tibiae in young male athletes. Bone 38:708–713

    Article  PubMed  Google Scholar 

  14. Falk B, Galili Y, Zigel L, Constantini N, Eliakim A (2007) A cumulative effect of physical training on bone strength in males. Int J Sports Med 28:449–455

    Article  PubMed  CAS  Google Scholar 

  15. Daly RM, Bass SL (2006) Lifetime sport and leisure activity participation is associated with greater bone size, quality and strength in older men. Osteoporos Int 17:1258–1267

    Article  PubMed  CAS  Google Scholar 

  16. Nurzenski MK, Briffa NK, Price RI, Khoo BC, Devine A, Beck TJ, Prince RL (2007) Geometric indices of bone strength are associated with physical activity and dietary calcium intake in healthy older women. J Bone Miner Res 22:416–424

    Article  PubMed  Google Scholar 

  17. Umemura Y, Baylink DJ, Wergedal JE, Mohan S, Srivastava AK (2002) A time course of bone response to jump exercise in C57BL/6J mice. J Bone Miner Metab 20:209–215

    Article  PubMed  Google Scholar 

  18. Hamrick MW, Skedros JG, Pennington C, McNeil PL (2006) Increased osteogenic response to exercise in metaphyseal versus diaphyseal cortical bone. J Musculoskelet Neuronal Interact 6:258–263

    PubMed  CAS  Google Scholar 

  19. Mori T, Okimoto N, Sakai A, Okazaki Y, Nakura N, Notomi T, Nakamura T (2003) Climbing exercise increases bone mass and trabecular bone turnover through transient regulation of marrow osteogenic and osteoclastogenic potentials in mice. J Bone Miner Res 18:2002–2009

    Article  PubMed  Google Scholar 

  20. Banu J, Bhattacharya A, Rahman M, O’Shea M, Fernandes G (2006) Effects of conjugated linoleic acid and exercise on bone mass in young male Balb/C mice. Lipids Health Dis 5:7

    Article  PubMed  CAS  Google Scholar 

  21. Peng ZQ, Vaananen HK, Tuukkanen J (1997) Ovariectomy-induced bone loss can be affected by different intensities of treadmill running exercise in rats. Calcif Tissue Int 60:441–448

    Article  PubMed  CAS  Google Scholar 

  22. Tuukkanen J, Koivukangas A, Jamsa T, Sundquist K, Mackay CA, Marks SC Jr (2000) Mineral density and bone strength are dissociated in long bones of rat osteopetrotic mutations. J Bone Miner Res 15:1905–1911

    Article  PubMed  CAS  Google Scholar 

  23. Cobayashi F, Lopes LA, Taddei JA (2005) Bone mineral density in overweight and obese adolescents. J Pediatr (Rio J) 81:337–342

    Google Scholar 

  24. Aubertin-Leheudre M, Lord C, Labonte M, Khalil A, Dionne IJ (2008) Relationship between sarcopenia and fracture risks in obese postmenopausal women. J Women Aging 20:297–308

    Article  PubMed  Google Scholar 

  25. Galusca B, Zouch M, Germain N, Bossu C, Frere D, Lang F, Lafage-Proust MH, Thomas T, Vico L, Estour B (2008) Constitutional thinness: unusual human phenotype of low bone quality. J Clin Endocrinol Metab 93:110–117

    Article  PubMed  CAS  Google Scholar 

  26. Brahmabhatt V, Rho J, Bernardis L, Gillespie R, Ziv I (1998) The effects of dietary-induced obesity on the biomechanical properties of femora in male rats. Int J Obes Relat Metab Disord 22:813–818

    Article  PubMed  CAS  Google Scholar 

  27. Cao JJ, Gregoire BR, Gao H (2009) High-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice. Bone 44:1097–1104

    Article  PubMed  CAS  Google Scholar 

  28. Hamrick MW, Ferrari SL (2008) Leptin and the sympathetic connection of fat to bone. Osteoporos Int 19:905–912

    Article  PubMed  CAS  Google Scholar 

  29. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197–207

    Article  PubMed  CAS  Google Scholar 

  30. Hamrick MW, Della-Fera MA, Choi YH, Pennington C, Hartzell D, Baile CA (2005) Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. J Bone Miner Res 20:994–1001

    Article  PubMed  CAS  Google Scholar 

  31. Hamrick MW, Ding KH, Ponnala S, Ferrari SL, Isales CM (2008) Caloric restriction decreases cortical bone mass but spares trabecular bone in the mouse skeleton: implications for the regulation of bone mass by body weight. J Bone Miner Res 23:870–878

    Article  PubMed  CAS  Google Scholar 

  32. Lorentzon M, Mellstrom D, Ohlsson C (2005) Association of amount of physical activity with cortical bone size and trabecular volumetric BMD in young adult men: the GOOD study. J Bone Miner Res 20:1936–1943

    Article  PubMed  Google Scholar 

  33. Iuliano-Burns S, Stone J, Hopper JL, Seeman E (2005) Diet and exercise during growth have site-specific skeletal effects: a co-twin control study. Osteoporos Int 16:1225–1232

    Article  PubMed  CAS  Google Scholar 

  34. Ma H, Leskinen T, Alen M, Cheng S, Sipila S, Heinonen A, Kaprio J, Suominen H, Kujala UM (2009) Long-term leisure time physical activity and properties of bone: a twin study. J Bone Miner Res 24:1427–1433

    Article  PubMed  Google Scholar 

  35. Plochocki JH, Rivera JP, Zhang C, Ebba SA (2008) Bone modeling response to voluntary exercise in the hindlimb of mice. J Morphol 269:313–318

    Article  PubMed  Google Scholar 

  36. Bourrin S, Genty C, Palle S, Gharib C, Alexandre C (1994) Adverse effects of strenuous exercise: a densitometric and histomorphometric study in the rat. J Appl Physiol 76:1999–2005

    PubMed  CAS  Google Scholar 

  37. Wallace JM, Rajachar RM, Allen MR, Bloomfield SA, Robey PG, Young MF, Kohn DH (2007) Exercise-induced changes in the cortical bone of growing mice are bone- and gender-specific. Bone 40:1120–1127

    Article  PubMed  Google Scholar 

  38. Warren GL, Moran AL, Hogan HA, Lin AS, Guldberg RE, Lowe DA (2007) Voluntary run training but not estradiol deficiency alters the tibial bone–soleus muscle functional relationship in mice. Am J Physiol Regul Integr Comp Physiol 293:R2015–R2026

    PubMed  CAS  Google Scholar 

  39. Luu YK, Capilla E, Rosen CJ, Gilsanz V, Pessin JE, Judex S, Rubin CT (2009) Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J Bone Miner Res 24:50–61

    Article  PubMed  CAS  Google Scholar 

  40. Kyung TW, Lee JE, Van Phan T, Yu R, Choi HS (2009) Osteoclastogenesis by bone marrow-derived macrophages is enhanced in obese mice. J Nutr 139:502–506

    Article  PubMed  CAS  Google Scholar 

  41. Halloran BP, Ferguson VL, Simske SJ, Burghardt A, Venton LL, Majumdar S (2002) Changes in bone structure and mass with advancing age in the male C57BL/6J mouse. J Bone Miner Res 17:1044–1050

    Article  PubMed  Google Scholar 

  42. Somerville JM, Aspden RM, Armour KE, Armour KJ, Reid DM (2004) Growth of C57BL/6 mice and the material and mechanical properties of cortical bone from the tibia. Calcif Tissue Int 74:469–475

    Article  PubMed  CAS  Google Scholar 

  43. Daly RM (2007) The effect of exercise on bone mass and structural geometry during growth. Med Sport Sci 51:33–49

    Article  PubMed  Google Scholar 

  44. Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, Palermo L, Scott J, Vogt TM (1993) Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet 341:72–75

    Article  PubMed  CAS  Google Scholar 

  45. Kanis JA (2002) Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359:1929–1936

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by the Academy of Finland (grant 124 037). H. M. was supported by the National Graduate School of Musculoskeletal Disorders and Biomaterials, Finland. We thank Leena-Kaisa Tulla and Erkki Helkala for their excellent technical assistance.

Author information

Authors and Affiliations

  1. Department of Health Sciences, University of Jyväskylä, P.O. Box 35 (LL), 40014, Jyväskylä, Finland

    Hongqiang Ma, Urho M. Kujala, Paavo Rahkila & Harri Suominen

  2. Department of Biology of Physical Activity, University of Jyväskylä, Jyväskylä, Finland

    Sira Torvinen, Mika Silvennoinen, Rita Rinnankoski-Tuikka & Heikki Kainulainen

  3. Pharmatest Services, Turku, Finland

    Jukka Morko & Zhiqi Peng

Authors
  1. Hongqiang Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sira Torvinen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mika Silvennoinen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rita Rinnankoski-Tuikka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Heikki Kainulainen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jukka Morko
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhiqi Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Urho M. Kujala
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Paavo Rahkila
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Harri Suominen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Harri Suominen.

Additional information

The authors declare no conflict of interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ma, H., Torvinen, S., Silvennoinen, M. et al. Effects of Diet-Induced Obesity and Voluntary Wheel Running on Bone Properties in Young Male C57BL/6J Mice. Calcif Tissue Int 86, 411–419 (2010). https://doi.org/10.1007/s00223-010-9346-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-010-9346-3

Keywords

Search

Navigation