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RESEARCH ARTICLE
Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice
Elise L. Donovan, Erika Barboza Prado Lopes, Albert Batushansky, Mike Kinter, Timothy M. Griffin
Disease Models & Mechanisms 2018 11: dmm034827 doi: 10.1242/dmm.034827 Published 31 August 2018
Elise L. Donovan
1Aging and Metabolism Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK 73104, USA
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Erika Barboza Prado Lopes
1Aging and Metabolism Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK 73104, USA
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Albert Batushansky
1Aging and Metabolism Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK 73104, USA
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Mike Kinter
1Aging and Metabolism Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK 73104, USA
2Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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Timothy M. Griffin
1Aging and Metabolism Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK 73104, USA
2Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
3Department of Biochemistry and Molecular Biology and Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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ABSTRACT

Obesity is one of the most significant risk factors for knee osteoarthritis. However, therapeutic strategies to prevent or treat obesity-associated osteoarthritis are limited because of uncertainty about the etiology of disease, particularly with regard to metabolic factors. High-fat-diet-induced obese mice have become a widely used model for testing hypotheses about how obesity increases the risk of osteoarthritis, but progress has been limited by variation in disease severity, with some reports concluding that dietary treatment alone is insufficient to induce osteoarthritis in mice. We hypothesized that increased sucrose content of typical low-fat control diets contributes to osteoarthritis pathology and thus alters outcomes when evaluating the effects of a high-fat diet. We tested this hypothesis in male C57BL/6J mice by comparing the effects of purified diets that independently varied sucrose or fat content from 6 to 26 weeks of age. Outcomes included osteoarthritis pathology, serum metabolites, and cartilage gene and protein changes associated with cellular metabolism and stress-response pathways. We found that the relative content of sucrose versus cornstarch in low-fat iso-caloric purified diets caused substantial differences in serum metabolites, joint pathology, and cartilage metabolic and stress-response pathways, despite no differences in body mass or body fat. We also found that higher dietary fat increased fatty acid metabolic enzymes in cartilage. The findings indicate that the choice of control diets should be carefully considered in mouse osteoarthritis studies. Our study also indicates that altered cartilage metabolism might be a contributing factor to how diet and obesity increase the risk of osteoarthritis.

Footnotes

  • Competing interests

    The authors declare no competing or financial interests.

  • Author contributions

    Conceptualization: E.L.D., T.M.G.; Methodology: E.L.D., M.K., T.M.G.; Software: A.B.; Validation: E.L.D., M.K., T.M.G.; Formal analysis: E.L.D., A.B., T.M.G.; Investigation: E.L.D., E.B.P.L., M.K.; Resources: M.K., T.M.G.; Writing - original draft: E.L.D., A.B., T.M.G.; Writing - review & editing: E.L.D., E.B.P.L., A.B., M.K., T.M.G.; Visualization: E.L.D., A.B., T.M.G.; Supervision: T.M.G.; Project administration: E.L.D.; Funding acquisition: M.K., T.M.G.

  • Funding

    This work was supported by the National Institutes of Health (NIH) (P20RR018758, P20GM103441, P30GM114731, P30AG050911 and R01AG049058) and the Arthritis Foundation (Arthritis Investigator Award to T.M.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Arthritis Foundation.

  • Supplementary information

    Supplementary information available online at http://dmm.biologists.org/lookup/doi/10.1242/dmm.034827.supplemental

  • Received April 5, 2018.
  • Accepted July 9, 2018.
  • © 2018. Published by The Company of Biologists Ltd
http://creativecommons.org/licenses/by/3.0

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Keywords

  • Osteoarthritis
  • Obesity
  • Cartilage
  • Metabolism
  • High-fat diet
  • Mouse

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RESEARCH ARTICLE
Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice
Elise L. Donovan, Erika Barboza Prado Lopes, Albert Batushansky, Mike Kinter, Timothy M. Griffin
Disease Models & Mechanisms 2018 11: dmm034827 doi: 10.1242/dmm.034827 Published 31 August 2018
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RESEARCH ARTICLE
Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice
Elise L. Donovan, Erika Barboza Prado Lopes, Albert Batushansky, Mike Kinter, Timothy M. Griffin
Disease Models & Mechanisms 2018 11: dmm034827 doi: 10.1242/dmm.034827 Published 31 August 2018

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