title: Prediabetes Enhances Periodontal Inflammation Consistent With Activation of Toll-Like Receptor-Mediated Nuclear Factor-κB Pathway in Rats.
abstract: Clinical studies have showed that prediabetes (preDM) is a predisposing factor for periodontitis. However, the pathogenic mechanism involved is unclear. Because it is known that the activation of Toll-like receptor (TLR)-mediated nuclear factor-kappa B (NF-κB) signaling pathway plays a crucial role in periodontitis, it is hypothesized that preDM enhances periodontal inflammation by activation of the TLR-mediated NF-κB pathway.
  
  
  
  In this study, a preDM rat model is established by feeding a high-fat diet (HFD). HFD-induced rats with preDM (n = 7) and normal chow-fed rats (n = 7) were studied. The animal model was characterized in terms of body weight and the glycemic and insulinemic profiles. The following parameters were assessed to evaluate possible early periodontal alterations and underlying mechanisms: 1) histology analysis of periodontal tissue; and 2) serum and mRNA levels and/or the tissue protein expression of TLRs, myeloid differentiation factor 88 (MyD88), tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), NF-κB, cytokines, advanced glucose ends (AGEs), and free fatty acids (FFAs).
  
  
  
  Rats with preDM presented higher expression of TLR2 and TLR4 in periodontal tissue in the HFD group compared with the control group. The TLR2 and TLR4 was mostly expressed in gingiva, and TLR4 was expressed in periodontal ligament in rats. Furthermore, the MyD88 and TRAF6 protein levels were significantly increased in gingiva in rats with preDM compared with normal rats. The activity of NF-κB signals was higher in rats with preDM than in normal rats. Regarding cytokines expression, the TNF-α protein levels and interleukin-1β mRNA levels were significantly increased in the HFD group compared with the control group. In the serum, AGEs levels were significantly increased in the rats with preDM. Mean FFAs concentrations were increased in rats with preDM compared with normal rats, but it did not reach statistical significance.
  
  
  
  In rats with preDM, TLR2 and TLR4 gene and protein levels were higher in periodontal tissue, and the activation of NF-κB may, through TLRs/MyD88, cause more cytokine secretion, which is associated with the onset or development of periodontal disease.
authors.affiliation: National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University.|Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Huang
authors.affiliation: National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University.|Department of Pedodontics, West China School of Stomatology, Sichuan University.
authors.forename: Weihua
authors.initials: W
authors.lastname: Guo
authors.affiliation: National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.affiliation: National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Chen
authors.affiliation: National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Sun
authors.affiliation: National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University.|Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University.
authors.forename: Xuexin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University.|Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University.
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
mesh_terms: D000818:Animals; D007249:Inflammation; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011236:Prediabetic State; D051381:Rats; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
keywords: Diet, high-fat; NF-kappa B; inflammation; prediabetic state; rats; toll-like receptors