Involvement of toll-like receptor 4 in alveolar bone loss and glucose homeostasis in experimental periodontitis

• Published in: Journal of periodontal research Vol. 46; no. 1; pp. 21 - 30
• Main Authors: Watanabe, K., Iizuka, T., Adeleke, A., Pham, L., Shlimon, A. E., Yasin, M., Horvath, P., Unterman, T. G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2011; Blackwell
• Subjects: alveolar bone; Alveolar Bone Loss - metabolism; Animals; Biological and medical sciences; Chronic Periodontitis - metabolism; Dentistry; diabetes; Diabetes. Impaired glucose tolerance; Dietary Fats - metabolism; Diseases of the osteoarticular system; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Glucose - metabolism; Glucose Tolerance Test; Homeostasis; inflammation; Insulin Resistance - genetics; Liver - metabolism; Male; Medical sciences; Mice; Mice, Inbred C3H; Mice, Knockout; Mice, Mutant Strains; Mutation; Non tumoral diseases; Osteoporosis. Osteomalacia. Paget disease; Otorhinolaryngology. Stomatology; periodontal disease; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Toll-Like Receptor 4 - deficiency; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Tumor Necrosis Factor-alpha - biosynthesis; Endocrinopathy; Stomatology; Diabetes mellitus; Diseases of the osteoarticular system; Alveolar bone; Homeostasis; Inflammation; Glucose; Periodontal disease; Periodontitis; diabetes; Osteopenia; Biological receptor
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1111/j.1600-0765.2010.01304.x

Watanabe K, Iizuka T, Adeleke A, Pham L, Shlimon AE, Yasin M, Horvath P, Unterman TG. Involvement of toll‐like receptor 4 in alveolar bone loss and glucose homeostasis in experimental periodontitis. J Periodont Res 2011; 46: 21–30. © 2010 John Wiley & Sons A/S Background and Objective:  There is general agreement that certain fatty acids and lipopolysaccharides (LPS) promote inflammation through toll‐like receptor 4 (TLR4), and that inflammation promotes insulin resistance. We therefore hypothesized that mice with periodontitis and a TLR4 loss‐of‐function (LOF) mutation fed a high‐fat (HF) diet would develop improved glucose homeostasis compared with wild‐type (WT) animals with periodontitis fed a HF diet. Material and Methods:  Wild‐type and TLR4 mutant mice fed a HF diet were divided into four groups (n = 6/group): WT; WT with periodontitis (WT/P); mutant (Mut); and mutant with periodontitis (Mut/P). Periodontitis was induced by placing LPS soaked ligatures around maxillary second molars. Fasting insulin and glucose levels were measured weekly for 10 wk. Glucose tolerance was evaluated at baseline (week 1) and at 9 wk. Insulin signaling (phosphorylation of Akt) and tumor necrosis factor‐α (TNF‐α) mRNA levels in liver were determined when the mice were killed at week 10. Results:  Mut/P mice developed less alveolar bone loss compared with WT/P mice (p < 0.05). Fasting glucose levels were improved after 8 wk of feeding a HF diet (weeks 9 and 10) in Mut/P mice compared with Mut, WT and WT/P mice (p < 0.05). Glucose tolerance was impaired in all groups compared with baseline (p < 0.05), except for the Mut/P group. Insulin signaling was improved (p < 0.05), and expression of TNF‐α was decreased (p < 0.05) in the liver of Mut/P mice compared with the liver of WT/P mice. Conclusion:  The TLR4 LOF mutation partially protects against alveolar bone loss and improves glucose homeostasis in mice with periodontitis fed a HF diet.