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Calcified Tissue International

, Volume 103, Issue 2, pp 217–226 | Cite as

The Time Point-Specific Effect of Beta-Adrenergic Blockade in Attenuating High Fat Diet-Induced Obesity and Bone Loss

  • Kyunghwa Baek
  • Jiho Kang
  • Jinu Lee
  • Min Kim
  • Jeong-Hwa Baek
Original Research

Abstract

We aimed to clarify the key factor determining the effect of beta blocker attenuating high fat diet- induced obesity and bone loss. Six-week-old C57BL/6 male mice were assigned to groups reflecting different relative onset of obesity and beta blocker administration, different diet (control vs. high fat), and treatment (vehicle vs. beta blocker: propranolol). Mice in Group 1 were fed a control diet (CON) or high fat diet (HIGH) with vehicle or propranolol for 12 weeks. Mice in Group 2 were fed a CON or HIGH without pharmaceutical treatment for the first 12 weeks, followed by another 12 weeks of treatment with vehicle or propranolol. Mice in Group 3 were fed a CON without pharmaceutical treatment for the first 12 weeks, followed by stratification into diet-based subgroups and another 12 weeks of treatment with vehicle or propranolol. Propranolol attenuated the HIGH-induced increase in body weight/fat mass in Group 1 mice and in Group 3 mice, but not in Group 2 mice. Propranolol mitigated HIGH-induced reduction in femoral trabecular bone mineral density and bone architecture deterioration in Group 1 mice but not in Group 2 mice. HIGH feeding in Group 3 did not compromise skeletal integrity. Taken together, propranolol attenuates HIGH-induced body weight increases while weight gain is in progress but not once obesity has already been established. HIGH feeding during the growth period results in compromised bone mass/architecture; which can be attenuated by propranolol administration during the growth period, but not by propranolol administration after obesity has already been established.

Keywords

Propranolol Beta-adrenergic receptor blockade Obesity Bone loss High fat diet 

Notes

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MEST) (2011-0016548, 2017R1A2B1006203).

Author contributions

KB and J‑HB designed the study. KB prepared the first draft of the paper. KB, JK, JL, and MK contributed to the experimental work. KB conducted the statistical analysis of the data. KB and J‑HB revised the paper critically for intellectual content and approved the final version. J‑HB is guarantor. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.

Compliance with Ethical Standards

Conflict of interest

Kyunghwa Baek, Jiho Kang, Jinu Lee, Min Kim and Jeong‑Hwa Baek declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Human and Animal Rights

All procedures performed in studies involving animals were in accordance with the ethical standards of Seoul National University Institutional Animal Care and Use Committee (SNU-110531-2).

Informed consent

Informed consent was obtained from all the authors of this manuscript.

References

  1. 1.
    Bjurholm A (1991) Neuroendocrine peptides in bone. Int Orthop 15:325–329CrossRefPubMedGoogle Scholar
  2. 2.
    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 111:305–317CrossRefPubMedGoogle Scholar
  3. 3.
    Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards WG, Bannon TW, Noda M, Clement K, Vaisse C, Karsenty G (2005) Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434:514–520CrossRefPubMedGoogle Scholar
  4. 4.
    Baek K, Bloomfield SA (2009) Beta-adrenergic blockade and leptin replacement effectively mitigate disuse bone loss. J Bone Miner Res 24:792–799CrossRefPubMedGoogle Scholar
  5. 5.
    Bonnet N, Beaupied H, Vico L, Dolleans E, Laroche N, Courteix D, Benhamou CL (2007) Combined effects of exercise and propranolol on bone tissue in ovariectomized rats. J Bone Miner Res 22:578–588CrossRefPubMedGoogle Scholar
  6. 6.
    Tatsumi S, Ito M, Asaba Y, Tsutsumi K, Ikeda K (2008) Life-long caloric restriction reveals biphasic and dimorphic effects on bone metabolism in rodents. Endocrinology 149:634–641CrossRefPubMedGoogle Scholar
  7. 7.
    da Silva AA, do Carmo J, Dubinion J, Hall JE (2009) The role of the sympathetic nervous system in obesity-related hypertension. Curr Hypertens Rep 11:206–211CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Baek K, Hwang HR, Park HJ, Kwon A, Qadir AS, Baek JH (2014) Propranolol, a beta-adrenergic antagonist, attenuates the decrease in trabecular bone mass in high calorie diet fed growing mice. BMB Rep 47:506–511CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Perez-Castrillon JL, De Luis DA, Duenas-Laita A (2009) Are beta-blockers useful in the prevention of osteoporotic fractures? Eur Rev Med Pharmacol Sci 13:157–162PubMedGoogle Scholar
  10. 10.
    Bonnet N, Gadois C, McCloskey E, Lemineur G, Lespessailles E, Courteix D, Benhamou CL (2007) Protective effect of beta blockers in postmenopausal women: influence on fractures, bone density, micro and macroarchitecture. Bone 40:1209–1216CrossRefPubMedGoogle Scholar
  11. 11.
    de Vries F, Souverein PC, Cooper C, Leufkens HG, van Staa TP (2007) Use of beta-blockers and the risk of hip/femur fracture in the United Kingdom and The Netherlands. Calcif Tissue Int 80:69–75CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Pasco JA, Henry MJ, Sanders KM, Kotowicz MA, Seeman E, Nicholson GC, Geelong Osteoporosis S (2004) Beta-adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density: Geelong Osteoporosis Study. J Bone Miner Res 19:19–24CrossRefPubMedGoogle Scholar
  13. 13.
    Rejnmark L, Vestergaard P, Mosekilde L (2006) Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study. J Hypertens 24:581–589CrossRefPubMedGoogle Scholar
  14. 14.
    Schlienger RG, Kraenzlin ME, Jick SS, Meier CR (2004) Use of beta-blockers and risk of fractures. Jama 292:1326–1332CrossRefPubMedGoogle Scholar
  15. 15.
    Schoo M, Sturkenboom M, Van Leeuwen J, Stricker B, Pols H (2005) Use of beta-blockers is associated with BMD and fracture risk. Bone. Elsevier Science Inc., New York, pp S129–S130Google Scholar
  16. 16.
    Levasseur R, Dargent-Molina P, Sabatier JP, Marcelli C, Breart G (2005) Beta-blocker use, bone mineral density, and fracture risk in older women: results from the Epidemiologie de l’Osteoporose prospective study. J Am Geriatr Soc 53:550–552CrossRefPubMedGoogle Scholar
  17. 17.
    Meisinger C, Heier M, Lang O, Doring A (2007) Beta-blocker use and risk of fractures in men and women from the general population: the MONICA/KORA Augsburg cohort study. Osteoporos Int 18:1189–1195CrossRefPubMedGoogle Scholar
  18. 18.
    Reid IR, Gamble GD, Grey AB, Black DM, Ensrud KE, Browner WS, Bauer DC (2005) Beta-blocker use, BMD, and fractures in the study of osteoporotic fractures. J Bone Miner Res 20:613–618CrossRefPubMedGoogle Scholar
  19. 19.
    Rejnmark L, Vestergaard P, Kassem M, Christoffersen BR, Kolthoff N, Brixen K, Mosekilde L (2004) Fracture risk in perimenopausal women treated with beta-blockers. Calcif Tissue Int 75:365–372CrossRefPubMedGoogle Scholar
  20. 20.
    Boxall BW, Clark AL (2012) Beta-blockers and weight change in patients with chronic heart failure. J Card Fail 18:233–237CrossRefPubMedGoogle Scholar
  21. 21.
    Rossner S, Taylor CL, Byington RP, Furberg CD (1990) Long term propranolol treatment and changes in body weight after myocardial infarction. Bmj 300:902–903CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Pischon T, Sharma AM (2001) Use of beta-blockers in obesity hypertension: potential role of weight gain. Obes Rev 2:275–280CrossRefPubMedGoogle Scholar
  23. 23.
    Dempster B (2013) National rationing of MRI in Australia has impact on use of CT. Bmj 346:f3929CrossRefPubMedGoogle Scholar
  24. 24.
    Parfitt AM (1987) Trabecular bone architecture in the pathogenesis and prevention of fracture. Am J Med 82:68–72CrossRefPubMedGoogle Scholar
  25. 25.
    Baek K, Bloomfield SA (2012) Blocking beta-adrenergic signaling attenuates reductions in circulating leptin, cancellous bone mass, and marrow adiposity seen with dietary energy restriction. J Appl Physiol 113:1792–1801CrossRefPubMedGoogle Scholar
  26. 26.
    Veldhuis-Vlug AG, Tanck MW, Limonard EJ, Endert E, Heijboer AC, Lips P, Fliers E, Bisschop PH (2015) The effects of beta-2 adrenergic agonist and antagonist on human bone metabolism: a randomized controlled trial. Bone 71:196–200CrossRefPubMedGoogle Scholar
  27. 27.
    Mundy GR (2007) Osteoporosis and inflammation. Nutr Rev 65:S147-151CrossRefGoogle Scholar
  28. 28.
    Wellen KE, Hotamisligil GS (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Investig 112:1785–1788CrossRefPubMedGoogle Scholar
  29. 29.
    Evans AL, Paggiosi MA, Eastell R, Walsh JS (2015) Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood. J Bone Miner Res 30:920–928CrossRefPubMedGoogle Scholar
  30. 30.
    Ionova-Martin SS, Wade JM, Tang S, Shahnazari M, Ager JW 3rd, Lane NE, Yao W, Alliston T, Vaisse C, Ritchie RO (2011) Changes in cortical bone response to high-fat diet from adolescence to adulthood in mice. Osteoporos Int 22:2283–2293CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmacology, College of Dentistry and Research Institute of Oral ScienceGangneung-Wonju National UniversityGangwondoRepublic of Korea
  2. 2.Department of Molecular Genetics, School of Dentistry and Dental Research InstituteSeoul National UniversitySeoulRepublic of Korea
  3. 3.Department of Molecular Genetics, School of Dentistry and Dental Research InstituteSeoul National UniversitySeoulRepublic of Korea

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