High-fat diet-induced metabolic syndrome increases ligature-induced alveolar bone loss in mice.

BACKGROUND: It has been well documented that metabolic syndrome (MetS) increases severity of periodontitis. In this study, we determined the effect of high-fat diet (HFD)-induced MetS on alveolar bone loss in a mouse model with ligature-induced periodontitis. To understand how MetS increases bone loss, we tested our hypothesis that palmitic acid (PA), a most abundant saturated fatty acid in the HFD, interacts with lipopolysaccharide (LPS) to promote osteoclastogenesis. METHODS: We induced MetS by feeding mice HFD for 18 weeks and induced periodontitis with ligature placement. After treatments, we assessed alveolar bone loss using micro-computed tomography and determined osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining. To explore the mechanisms, we treated macrophages with PA, LPS or both and analyzed the osteoclast formation and cytokine expression in macrophages. RESULTS: While ligature robustly induced periodontitis in mice with or without MetS, the mice with MetS had more bone loss than those without MetS. PA and LPS cooperatively induced osteoclast formation and stimulated the expression of inflammatory cytokines involved in osteoclastogenesis potentially via a FAT/CD36-dependent mechanism in macrophages. CONCLUSIONS: HFD-induced MetS increases alveolar bone loss in mice with ligature-induced periodontitis, and PA and LPS cooperatively stimulate osteoclast formation and proinflammatory gene expression in macrophages.