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High-Fat Diet Causes Bone Loss in Young Mice by Promoting Osteoclastogenesis Through Alteration of the Bone Marrow Environment

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Abstract

Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks of HFD treatment. After 6 and 12 weeks, HFD-exposed mice had less bone mass and increased osteoclast numbers. Bone marrow cells, but not spleen cells, from HFD-fed mice had increased osteoclast precursor frequency, elevated osteoclast formation, and bone resorption activity, as well as increased expression of osteoclastogenic regulators including RANKL, TNF, and PPAR-gamma. Bone formation rate and osteoblast and adipocyte numbers were also increased in HFD-fed mice. Isolated bone marrow cells also had a corresponding elevation in the expression of positive regulators of osteoblast and adipocyte differentiation. Our findings indicate that in juvenile mice, HFD-induced bone loss is mainly due to increased osteoclast bone resorption by affecting the bone marrow microenvironment. Thus, targeting osteoclast formation may present a new therapeutic approach for bone complications in obese children.

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Acknowledgments

The authors thank Y. Li for technical assistance with the slide scanner and E. Henderson for help with manuscript editing. Research was supported by Grants from National Institute of Health PHS awards (AR48697 and AR63650 to LX, AR43510 to BFB, T32 ES07026 to EB, P01 ES011854 and P30 ES301247 to JEP).

Conflict of interest

The authors Lei Shu, Eric Beier, Tzong Sheu, Hengwei Zhang, Michael J. Zuscik, Edward J. Puzas, Brendan F. Boyce, Robert A. Mooney, and Lianping Xing declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

The Institutional Animal Care and Use Committee approved of all animal care and experimentation.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, Rochester, NY, 14642, USA

    Lei Shu, Hengwei Zhang, Brendan F. Boyce, Robert A. Mooney & Lianping Xing

  2. Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Eric Beier, Tzong Sheu, Michael J. Zuscik, Edward J. Puzas, Brendan F. Boyce, Robert A. Mooney & Lianping Xing

  3. Division of Geriatric Endocrinology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China

    Lei Shu

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  1. Lei Shu
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Correspondence to Robert A. Mooney or Lianping Xing.

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Lei Shu and Eric Beier are Co-first authors.

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Shu, L., Beier, E., Sheu, T. et al. High-Fat Diet Causes Bone Loss in Young Mice by Promoting Osteoclastogenesis Through Alteration of the Bone Marrow Environment. Calcif Tissue Int 96, 313–323 (2015). https://doi.org/10.1007/s00223-015-9954-z

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  • DOI: https://doi.org/10.1007/s00223-015-9954-z

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