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Background  Obesity is a leading risk factor for osteoarthritis (OA). In contrast, calorie restriction (CR) may lessen OA due to improved systemic inflammatory status and reduced weight-bearing. The aim of this study was to determine how CR with regular chow versus a high-fat diet (HFD) alters OA progression using the Hartley guinea pig model of disease.    Methods  Twenty-four male guinea pigs were allocated to four groups at 2 months of age: (1) ad libitum regular chow (obese), (2) CR regular chow (lean), (3) ad libitum HFD, and (4) CR HFD. Animals in both HFD groups ate identical amounts and were combined into one HFD group for analyses. At 5 months, hind limbs were harvested for microcomputed tomography (microCT) and histopathologic evaluation of knee OA. Total body, gonad fat, and infrapatellar fat pad (IFP) masses were recorded. IFPs were collected for gene expression analysis. Immunohistochemistry for monocyte chemoattractant protein-1 (MCP-1) was performed on intact joints. Serum was utilized for protein C3 measurement. All data were compared using ordinary one-way ANOVA analyses with Tukey’s post-hoc tests.    Results  Body mass in the lean and HFD groups were similar and lower than the obese group. Despite this, gonad fat pads in the HFD group were comparable to the obese group. MicroCT and histologic OA scores were similar in obese and HFD groups; both scores were significantly lower in the lean group. Obese and HFD groups displayed increased gene expression of pro-inflammatory and catabolic mediators in IFPs relative to lean animals. Consistent with this, immunohistochemistry for MCP-1 in knee joints demonstrated strong positive staining in obese and HFD groups but was minimally detected in lean animals. Serum protein C3 levels were also statistically higher.    Conclusions  This study demonstrated that CR with a regular chow diet lessened knee OA in the Hartley guinea pig and was associated with decreased local and systemic inflammation compared to obese animals. HFD animals, although under CR conditions, had OA scores and inflammatory markers similar to obese animals. Thus, diet composition, and not solely body weight, may be a key factor in development of OA.    Electronic supplementary material  The online version of this article (10.1186/s13075-019-1925-8) contains supplementary material, which is available to authorized users.

Calorie restriction with regular chow, but not a high-fat diet, delays onset of spontaneous osteoarthritis in the Hartley guinea pig model