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Animal Models

Diet-induced obesity alters the differentiation potential of stem cells isolated from bone marrow, adipose tissue and infrapatellar fat pad: the effects of free fatty acids

International Journal of Obesity volume 37, pages 1079–1087 (2013)Cite this article

Subjects

Abstract

Introduction:

Obesity is a major risk factor for several musculoskeletal conditions that are characterized by an imbalance of tissue remodeling. Adult stem cells are closely associated with the remodeling and potential repair of several mesodermally derived tissues such as fat, bone and cartilage. We hypothesized that obesity would alter the frequency, proliferation, multipotency and immunophenotype of adult stem cells from a variety of tissues.

Materials and Methods:

Bone marrow-derived mesenchymal stem cells (MSCs), subcutaneous adipose-derived stem cells (sqASCs) and infrapatellar fat pad-derived stem cells (IFP cells) were isolated from lean and high-fat diet-induced obese mice, and their cellular properties were examined. To test the hypothesis that changes in stem cell properties were due to the increased systemic levels of free fatty acids (FFAs), we further investigated the effects of FFAs on lean stem cells in vitro.

Results:

Obese mice showed a trend toward increased prevalence of MSCs and sqASCs in the stromal tissues. While no significant differences in cell proliferation were observed in vitro, the differentiation potential of all types of stem cells was altered by obesity. MSCs from obese mice demonstrated decreased adipogenic, osteogenic and chondrogenic potential. Obese sqASCs and IFP cells showed increased adipogenic and osteogenic differentiation, but decreased chondrogenic ability. Obese MSCs also showed decreased CD105 and increased platelet-derived growth factor receptor α expression, consistent with decreased chondrogenic potential. FFA treatment of lean stem cells significantly altered their multipotency but did not completely recapitulate the properties of obese stem cells.

Conclusions:

These findings support the hypothesis that obesity alters the properties of adult stem cells in a manner that depends on the cell source. These effects may be regulated in part by increased levels of FFAs, but may involve other obesity-associated cytokines. These findings contribute to our understanding of mesenchymal tissue remodeling with obesity, as well as the development of autologous stem cell therapies for obese patients.

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Acknowledgements

We thank Nancy Martin of the Flow Cytometry Shared Resource of the Duke Cancer Institute, as well as Steve Johnson of Orthopaedic Research Laboratories for assistance with animal handling. This study was supported by Taiwan GSSA graduate fellowship, NIH Grants AR50245, AG15768, AR48852, AR48182, the Arthritis Foundation, the Howard Hughes Medical Institute and a NSF graduate fellowship.

Author contributions

CLW planned and performed the experiments and wrote the paper; BOD assisted with cell isolations; DJ assisted and performed the experiments; FG conceived of the experiments, directed the project and wrote the paper.

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Authors and Affiliations

  1. Departments of Orthopaedic Surgery and Biomedical Engineering, Duke University Medical Center, Durham, NC, USA

    C-L Wu, B O Diekman, D Jain & F Guilak

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  1. C-L Wu
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  2. B O Diekman
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Correspondence to F Guilak.

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Wu, CL., Diekman, B., Jain, D. et al. Diet-induced obesity alters the differentiation potential of stem cells isolated from bone marrow, adipose tissue and infrapatellar fat pad: the effects of free fatty acids. Int J Obes 37, 1079–1087 (2013). https://doi.org/10.1038/ijo.2012.171

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