The effects of a high-fat diet on cartilage in the femoro-tibial joint of young adult rats

Abstract

Obesity is a major risk factor in the development of many diseases, including those of the musculoskeletal system such as osteoarthritis (OA). Recent studies of the knee joint of severally obese children detected articular cartilage (AC) lesions, the significance of which, in long-term risks of OA in adults, is not known. Using a rat model, this thesis project aimed to test the hypothesis that a high-fat (HF) diet would result in abnormalities in the femoro-tibial joint (FTJ) cartilages. It also examined the potential effect of exercise in preventing the effects of diet-induced obesity on FTJ cartilage. Upon weaning, 40 male Sprague-Dawley rats were fed a Chow (18% kal fat) or HF (45% kcal fat) diet. At 63 days half of each group was allocated to either spontaneous cage activity (SED) or to free access to an exercise wheel (EX), resulting in 4 groups (Chow-SED, HF-SED, Chow-EX, HF-EX). Body composition was assessed using dual-energy X-ray absorptiometry (DEXA), and fasting plasma leptin and insulin concentrations using ELISA. Femoro-tibial joint samples were processed for histological examination, stained with toluidine blue, and assessed for cartilage abnormalities. Epiphyseal growth cartilage (EGC) was graded using a modified cartilage grading protocol. Type X collagen within the EGC was assessed using immunohistochemistry. Pearson’s correlation was conducted between body composition, leptin concentration and the presence of cartilage abnormalities. Body mass, percentage body fat, and fasting plasma leptin and insulin concentrations were higher in HF than Chow-fed animals, and lower in exercised than in nonexercised animals. There was no evidence that HF diet or exercise was associated with hyaline articular cartilage (HAC) abnormality. Epiphyseal growth cartilage abnormalities consistent with the disease osteochondrosis (OC) were observed. There were significantly greater numbers of osteochondritic lesions in HF-SED and HF-EX animals compared to Chow control groups. Type X collagen staining was also present within the abnormalities of the epiphyseal cartilage, consistent with a disruption in endochondral ossification. Body weight (p=0.006), percentage body fat (p=0.002) and fasting plasma leptin concentration (p=0.027) were significantly correlated with the presence of abnormalities in the epiphyseal growth cartilage. This is the first known study to observe abnormalities in the EGC of young adult rats exposed to a HF diet. Both the mechanism leading to the formation of osteochondral defects in the young rat, and features of a HF diet that appear to exacerbate formation of EGC abnormalities need to be established before translation and comparison to cartilage lesions in young people can be achieved.