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Dis Model Mech. 2018 Aug 31;11(9). pii: dmm034827. doi: 10.1242/dmm.034827.

Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice.

Author information

1
Aging and Metabolism Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK 73104, USA.
2
Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
3
Aging and Metabolism Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK 73104, USA Tim-Griffin@omrf.org.
4
Department of Biochemistry and Molecular Biology and Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.

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.

KEYWORDS:

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

PMID:
30018076
PMCID:
PMC6176996
DOI:
10.1242/dmm.034827
[Indexed for MEDLINE]
Free PMC Article

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