PMID- 31196172 OWN - NLM STAT- MEDLINE DCOM- 20200529 LR - 20231012 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 21 IP - 1 DP - 2019 Jun 13 TI - Calorie restriction with regular chow, but not a high-fat diet, delays onset of spontaneous osteoarthritis in the Hartley guinea pig model. PG - 145 LID - 10.1186/s13075-019-1925-8 [doi] LID - 145 AB - 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. FAU - Radakovich, Lauren B AU - Radakovich LB AD - Department of Microbiology, Immunology, Pathology, Colorado State University, 200 West Lake Street, Fort Collins, CO, 80521, USA. FAU - Marolf, Angela J AU - Marolf AJ AD - Department of Environmental and Radiological Health Sciences, Colorado State University, 123 Flint Cancer Center, Fort Collins, CO, 80523, USA. FAU - Culver, Lauren A AU - Culver LA AD - Department of Microbiology, Immunology, Pathology, Colorado State University, 200 West Lake Street, Fort Collins, CO, 80521, USA. FAU - Santangelo, Kelly S AU - Santangelo KS AUID- ORCID: 0000-0002-2348-594X AD - Department of Microbiology, Immunology, Pathology, Colorado State University, 200 West Lake Street, Fort Collins, CO, 80521, USA. Kelly.Santangelo@colostate.edu. LA - eng GR - P30 CA046934/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20190613 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (Chemokine CCL2) SB - IM MH - *Animal Feed MH - Animals MH - Caloric Restriction/*methods MH - Chemokine CCL2/metabolism MH - Diet, High-Fat/*adverse effects MH - Disease Models, Animal MH - Disease Progression MH - Guinea Pigs MH - Knee Joint/*diagnostic imaging/metabolism MH - Male MH - Osteoarthritis, Knee/diagnosis/*diet therapy/physiopathology MH - Weight-Bearing/physiology MH - X-Ray Microtomography PMC - PMC6567638 OTO - NOTNLM OT - Calorie restriction OT - Hartley guinea pig OT - High-fat diet OT - Obesity OT - Osteoarthritis COIS- The authors declare that they have no competing interests. EDAT- 2019/06/15 06:00 MHDA- 2020/05/30 06:00 PMCR- 2019/06/13 CRDT- 2019/06/15 06:00 PHST- 2018/11/02 00:00 [received] PHST- 2019/05/23 00:00 [accepted] PHST- 2019/06/15 06:00 [entrez] PHST- 2019/06/15 06:00 [pubmed] PHST- 2020/05/30 06:00 [medline] PHST- 2019/06/13 00:00 [pmc-release] AID - 10.1186/s13075-019-1925-8 [pii] AID - 1925 [pii] AID - 10.1186/s13075-019-1925-8 [doi] PST - epublish SO - Arthritis Res Ther. 2019 Jun 13;21(1):145. doi: 10.1186/s13075-019-1925-8.