Effects of exercise on periodontal health and systemic changes in obese mice

Abstract

Periodontitis is a chronic inflammatory disease caused by opportunistic gram-negative bacteria. Increasing studies revealed obesity might be a risk indicator of periodontitis as overactivated adipose tissue may negatively influence bone remodeling and systemic health. The underlying mechanism, however, remains unclear. Exercise training exerts protective effects on obesity-related chronic diseases. The objectives of this study are, therefore, 1) to investigate the role of obesity in periodontal health, 2) to investigate the impact of exercise on the negative effects of obesity in alveolar bone remodeling and its possible mechanism in an animal model. Eight-week-old C57BL/6J male mice followed the consumption of high-fat diet (HFD, 45% kcal% fat) or low-fat diet (LFD, 10% kcal% fat) ad libitum for 4, 8, 12, 16 and 20 weeks. Then another eight-week-old mice were assigned 4-week (5 days/week) exercise training and different diets (HFD/LFD): sedentary with HFD/LFD (HS/LS); moderate-intensity exercise with HFD (HM); or high-intensity exercise with HFD/LFD (HH/LH). Serum and multiple tissues were harvested and tested at study endpoints. One-way analysis of variance followed by Bonferroni post hoc tests was carried out. The mice assigned to different groups (diet/exercise) consumed similar quality of food. Body weight and body fat increased over time under HFD, and HH group showed significantly attenuated weight gain and fat accumulation. Glucose tolerance and insulin sensitivity were impaired after HFD, while HH mice showed significantly better glycemic control. HS mice showed multiple organ changes, i.e. liver fat infiltration and hypertrophied adipocytes, with reduced changes in HH group. HS mice showed an increased apical-coronal distance from alveolar crest to cemento-enamel junction (dAcCej) between the mandibular first (M1) and second (M2) molars, as well as a reduction in bone mineral density (BMD) at M1 and M2 furcation area. HH mice suffered from less dAcCej and appeared with better BMD at M1/M2 furcations and tibia metaphysis. Bone resorption and osteoclastic activity were detectable in HS jaw and tibia. Mice serum fatty acids and selected obesity-related cytokines/factors were characterized: three saturated fatty acids (palmitic acid, stearic acid and hexanoic acid), one monounsaturated fatty acid (transgondoic acid), two poly-unsaturated fatty acids (arachidonic acid and DGLA), two adipose endocrines (leptin and FGF21), and two adipose factors (MMP-9 and Dkk-1) were significantly associated with dAcCej or BMD (M1 furcation or tibia). The effects of typical fatty acids on human periodontal ligament stem cells (hPDLSCs) were studied. 0.025 mM palmitic acid appeared to inhibit osteogenic differentiation of PDLSCs, while 0.1 mM oleic acid showed a positive effect on the osteogenesis. In conclusion, disruptive bone homeostasis was observed in an obese mouse model. High-intensity exercise alone attenuated in part the negative systemic impacts of obesity on bone metabolism, including periodontal supporting bones. Major adipose endocrines in serum like leptin, FGF21 and a few fatty acids were found to be associated with reduced tibia and dental BMD. Weight control, proper nutrition and regular exercise perhaps are needed to prevent disruptive bone homeostasis, especially for those who are obese or at risk for periodontitis.