Obesity-associated gingival vascular inflammation and insulin resistance

Obesity is a risk factor for periodontitis,but the pathogenic mechanism involved is unclear. we studied the effects of insulin in periodontal tissues during the state of obesity-induced insulin resistance. gingival samples were collected from fatty (zf) and lean (zl,control) zucker rats. endothelial nitric oxide synthase (enos) expression was decreased,and activities of protein kinase c (pkc) α,β2,δ,and ε isoforms were significantly increased in the gingiva from zf rats compared with those from zl rats. expression of oxidative stress markers (mrna) and the p65 subunit of nf-κb was significantly increased in zf rats. immunohistochemistry revealed that nf-κb activation was also increased in the gingival endothelial cells from transgenic mice overexpressing nf-κb-dependent enhanced green fluorescent protein (gfp) and on a high-fat vs. normal chow diet. analysis of the gingiva showed that insulin-induced phosphorylation of irs-1,akt,and enos was significantly decreased in zf rats,but erk1/2 activation was not affected. general pkc inhibitor and an anti-oxidant normalized the action of insulin on akt and enos activation in the gingiva from zf rats. this provided the first documentation of obesity-induced insulin resistance in the gingiva. analysis of our data suggested that pkc activation and oxidative stress may selectively inhibit insulin-induced akt and enos activation,causing endothelial dysfunction and inflammation. © international & american associations for dental research.