title: High-fat diet induces periodontitis in mice through lipopolysaccharides (LPS) receptor signaling: protective action of estrogens.
abstract: BACKGROUND
  A fat-enriched diet favors the development of gram negative bacteria in the intestine which is linked to the occurrence of type 2 diabetes (T2D). Interestingly, some pathogenic gram negative bacteria are commonly associated with the development of periodontitis which, like T2D, is characterized by a chronic low-grade inflammation. Moreover, estrogens have been shown to regulate glucose homeostasis via an LPS receptor dependent immune-modulation. In this study, we evaluated whether diet-induced metabolic disease would favor the development of periodontitis in mice. In addition, the regulatory role of estrogens in this process was assessed.
  
  
  METHODS
  Four-week-old C57BL6/J WT and CD14 (part of the TLR-4 machinery for LPS-recognition) knock-out female mice were ovariectomised and subcutaneously implanted with pellets releasing either placebo or 17β-estradiol (E2). Mice were then fed with either a normal chow or a high-fat diet for four weeks. The development of diabetes was monitored by an intraperitoneal glucose-tolerance test and plasma insulin concentration while periodontitis was assessed by identification of pathogens, quantification of periodontal soft tissue inflammation and alveolar bone loss.
  
  
  RESULTS
  The fat-enriched diet increased the prevalence of periodontal pathogenic microbiota like Fusobacterium nucleatum and Prevotella intermedia, gingival inflammation and alveolar bone loss. E2 treatment prevented this effect and CD14 knock-out mice resisted high-fat diet-induced periodontal defects.
  
  
  CONCLUSIONS
  Our data show that mice fed with a diabetogenic diet developed defects and microflora of tooth supporting-tissues typically associated with periodontitis. Moreover, our results suggest a causal link between the activation of the LPS pathway on innate immunity by periodontal microbiota and HFD-induced periodontitis, a pathophysiological mechanism that could be targeted by estrogens.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Blasco-Baque
authors.forename: Matteo
authors.initials: M
authors.lastname: Serino
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Vergnes
authors.forename: Elodie
authors.initials: E
authors.lastname: Riant
authors.forename: Pascale
authors.initials: P
authors.lastname: Loubieres
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Arnal
authors.forename: Pierre
authors.initials: P
authors.lastname: Gourdy
authors.forename: Michel
authors.initials: M
authors.lastname: Sixou
authors.forename: Rémy
authors.initials: R
authors.lastname: Burcelin
authors.forename: Philippe
authors.initials: P
authors.lastname: Kemoun
mesh_terms: D000818:Animals; D001862:Bone Resorption; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D016967:Fusobacterium nucleatum / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007249:Inflammation; D007328:Insulin / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008334:Mandible / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010518:Periodontitis / Q000378:metabolism* / Q000473:pathology; D018713:Prevotella intermedia / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004967:Estrogens; D007328:Insulin; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D004958:Estradiol; D005947:Glucose