Obesity-associated Gingival Vascular Inflammation and Insulin Resistance

Abstract

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, ß2, 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.

Obesity and oxidative stress in patients with different periodontal status: a case–control study

“…Thus, it might be argued that a more pro‐oxidative state and diminished antioxidant capacity in obese individuals could facilitate the onset of an aggravated periodontal‐disease process. This argument is in line with the increase in production of reactive oxygen species in periodontal tissue of obese animals found in the previously mentioned experimental studies .…”

“…This idea is supported by numerous previous studies that have assessed obesity as a state of ‘increased chronic oxidative stress’ . For example, one experimental animal study reported obesity to produce an exaggerated inflammatory response that was a contributing factor in periodontal tissue destruction of rats with experimental periodontitis , and two other studies with rats suggested that obesity can cause tissue to exhibit an exaggerated inflammatory response . Moreover, several studies have reported obesity to be associated with an increase in OS markers and a decrease in antioxidants, which could potentially increase the severity of tissue destruction caused by periodontal disease .…”

Persimmon vinegar ripening with the mountain-cultivated ginseng ingestion reduces blood lipids and lowers inflammatory cytokines in obese adolescents

“…NFκB is believed to have a direct relationship with the decrease in fat quantity, because there was a significant decrease in PV and MPV. In other words, the existing studies support the result of this study, as follows: NFκB concentration of an obese rat has the tendency of increasing compared to a rat with normal weight [ 58 ]; and the NFκB of an obese rat on high fat diet was significantly higher than the NFκB of a rat with normal weight [ 59 ]. However, it is believed that there is another reason, because the CON group had increase in NFκB concentration; while there was no change in fat quantity from before the test.…”

Metabolic Syndrome Exacerbates Inflammation and Bone Loss in Periodontitis

“…We demonstrated that LPS-induced alveolar bone loss in Zucker fat rats was more severe than that in control lean rats (Jin, Machado, et al 2014). Interestingly, Mizutani et al (2014) showed that the gingival tissue had increased activities of protein kinase C isoforms and expression of p65 subunit of nuclear factor kappa-B in Zucker fat rats without induction of periodontitis, suggesting that MetS per se is associated with a hyperinflammatory state in gingival tissue that may contribute to MetS-related periodontitis. Furthermore, Amar et al (2007) employed a mouse model with high-fat diet (HFD)-induced obesity (DIO) and Porphyromonas gingivalis (P. gingivalis)-induced periodontitis, demonstrating that DIO was associated with a higher degree of alveolar bone loss.…”