title: Involvement of toll-like receptor 4 in alveolar bone loss and glucose homeostasis in experimental periodontitis.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  The TLR4 LOF mutation partially protects against alveolar bone loss and improves glucose homeostasis in mice with periodontitis fed a HF diet.
authors.affiliation: Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612-7212, USA. keiko@uic.edu
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Iizuka
authors.forename: A
authors.initials: A
authors.lastname: Adeleke
authors.forename: L
authors.initials: L
authors.lastname: Pham
authors.forename: A E
authors.initials: AE
authors.lastname: Shlimon
authors.forename: M
authors.initials: M
authors.lastname: Yasin
authors.forename: P
authors.initials: P
authors.lastname: Horvath
authors.forename: T G
authors.initials: TG
authors.lastname: Unterman
mesh_terms: D016301:Alveolar Bone Loss / Q000378:metabolism*; D000818:Animals; D055113:Chronic Periodontitis / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009154:Mutation; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004041:Dietary Fats; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose