title: Metabolic syndrome exacerbates inflammation and bone loss in periodontitis.
abstract: Clinical studies have shown that metabolic syndrome (MetS) is associated with increased risk of developing periodontitis. However, the underlying mechanisms remain largely unknown. Since it is known that lipopolysaccharide (LPS)-activated toll-like receptor 4 signaling pathways play a crucial role in periodontitis, we hypothesized that MetS enhances LPS-induced periodontal inflammation and alveolar bone loss. In this study, we induced MetS in C57BL/6 mice by feeding them high-fat diet (HFD), and we induced periodontitis by periodontal injection of Aggregatibacter actinomycetemcomitans LPS. We found that mice fed a HFD had significantly increased body weight, plasma lipids, insulin, and insulin resistance when compared with mice fed regular chow, indicating that the mice developed MetS. We also found that a HFD markedly increased LPS-induced alveolar bone loss, osteoclastogenesis, and inflammatory infiltration. Analysis of gene expression in periodontal tissue revealed that HFD and LPS injection cooperatively stimulated expression of cytokines that are known to be involved in periodontal tissue inflammation and osteoclastogenesis-such as interleukin 6, monocyte-chemotactic protein 1, receptor activator of nuclear factor kappa-B ligand, and macrophage colony-stimulating factor. To further understand the potential mechanisms involved in MetS-boosted tissue inflammation, our in vitro studies showed that palmitic acid-the most abundant saturated fatty acid (SFA) and the major SFA in the HFD used in our animal study-potently enhanced LPS-induced proinflammatory gene expression in macrophages. In sum, this study demonstrated that MetS was associated with increased periodontal inflammation and alveolar bone loss in an LPS-induced periodontitis animal model. This study also suggests that SFA palmitic acid may play an important role in MetS-associated periodontitis by enhancing LPS-induced expression of inflammatory cytokines in macrophages.
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Kirkwood
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC, USA Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Lopes-Virella
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC, USA Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC, USA Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA huangyan@musc.edu.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000502:physiology; D016301:Alveolar Bone Loss / Q000382:microbiology / Q000503:physiopathology*; D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000097:blood / Q000209:etiology; D006946:Hyperinsulinism / Q000097:blood / Q000209:etiology; D007249:Inflammation; D007333:Insulin Resistance / Q000502:physiology; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000009:adverse effects; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis; D008264:Macrophages / Q000187:drug effects; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009765:Obesity / Q000097:blood / Q000209:etiology; D010010:Osteoclasts / Q000502:physiology; D019308:Palmitic Acid / Q000494:pharmacology; D010518:Periodontitis / Q000382:microbiology / Q000503:physiopathology*; D053245:RANK Ligand / Q000032:analysis
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D019308:Palmitic Acid; D016173:Macrophage Colony-Stimulating Factor
keywords: cytokines; gene expression; high-fat diet; lipopolysaccharide; osteoclast; palmitic acid