Adiponectin in Periodontitis: A Narrative Review of Biology, Human Evidence, Mechanistic Models and Translational...

Periodontitis is a chronic inflammatory disease which is initiated by dysbiotic biofilms and maintained by a host who is permissive to inflammation resulting in continuous destruction of periodontal supporting structures. Periodontitis occurs frequently with obesity and type 2 diabetes mellitus and the broader cardiometabolic risk state leading to investigations into the common immunometabolic pathways that link these conditions. Adiponectin, an insulin sensitizing and anti-inflammatory adipokine which can also act as a vasculoprotective and bone-related factor, has been studied as a potential modulator of the relation between periodontal inflammation and systemic metabolic disturbance. This narrative review summarizes the biology of adiponectin and its receptors, human findings relating to both the local and circulating forms of adiponectin in periodontal health and disease, the mechanism in cell and animal models and translational implications and limitations. The literature was reviewed in a narrative manner with particular attention to study quality, compartment-specific biology and any conflicts in evidence and the difference between biological plausibility and clinical relevance. A tendency for a reduction in the circulating, saliva and gingival crevicular fluid levels of adiponectin in periodontitis in human studies, particularly those with co-existing obesity and type 2 diabetes mellitus, can be demonstrated but these finding are often disparate due to variable methods in case definitions, assay techniques, metabolic background of subjects and other confounders. Experimental findings may establish biological plausibility by linking adiponectin signalling with the mechanisms which affect inflammatory responses, endothelial function and matrix homeostasis, osteoclastogenesis and subsequent alveolar bone loss, although adiponectin signalling appears context-specific in its actions and this does not confirm clinical relevance. Evidence suggests adiponectin is a biologically significant, but context-dependent factor within the immunometabolic network which connects periodontal disease with the systemic condition, rather than a sole marker or clinically recognized target for therapeutic intervention.