The clear relationship between obesity and periodontitis is well documented[64–92]. Overweight is a clear risk factor for the onset of T2D and CVD, as well as for respiratory and pressure disorders, osteoarthritis, reproductive abnormality, hepatitis, and some types of cancer. Adipocytes of fat tissue show the ability to secrete adipocytokines, which seem to be very important in controlling appetite and body weight. One of these cytokines is leptin, which shows a protective role against obesity. In fact, a condition of clear obesity can be also defined as a situation of leptin resistance with a consequent leptinemia.
Adipocytes can secrete other cytokines such as adiponectin and resistin. Serum adiponectin remains constant in normal condition but decreases in the presence of diabetes, obesity, insulin resistance, and CVD. Resistin shows a great proinflammatory role, and from studies conducted on mice it seems associated with insulin resistance[17, 22].
However, many researches affirm that the most important mediator related with obesity and insulin resistance is TNF-α, expressed plentifully in adipose tissue, in obese individuals with severe insulin resistance, and in neoplastic patients[67, 68]. Both TNF-α and Il-6, secreted by adipose cells, seem to trouble intracellular signaling, cause insulin resistance, and stimulate hepatic production of phase acute-phase proteins such as CRP. Recent murine studies show that the direct infusion of TNF-α or LPS, a TNF-α inductor, can cause a severe insulin resistance; by contrast, mice missing TNF-α or its receptor-codifying gene and submitted to a fatty diet appeared protected against insulin resistance compared with controls in the same condition having genes. It seems that when insulin binds its tissular receptor, a receptor tyrosine residue on the cytoplasmatic portion is autophosphorylated. The tyrosine residue of the cytoplasmatic insulin-receptor substrate (IRS-1) binding insulin receptor is phosphorylated and causes an intracellular signaling, which leads to the membrane recruitment of intracellular transporter of glucose, GLUT-4, to trap glucose molecules. TNF-α seems to be able to phosphorylate a serine residue on IRS-1 and, subsequently, to inhibit phosphorylation of either the insulin receptor or IRS-1.
Phosphorylation on IRS-1 can also prevent IRS-1 Tyr phosphorylation on adipocytes.
Other authors have supposed that TNF-α can interact with RNA transcription codifying for IRS-1 and GLUT 4, compromising their stability. It could also prevent Tyr phosphorylation of the insulin receptor, inducing hydrogen peroxide formation[22, 72].
Regarding the relationship between periodontitis and obesity, recent studies have demonstrated how normal-weight persons who participate in sports and physical activity show a decreased incidence of periodontal disease[73–76]. Recent studies have also demonstrated how individuals with normal weight showed a lower prevalence of periodontitis, decreased plasma levels of inflammatory markers, and increased insulin sensitivity. It is of note that during the development of periodontitis, in the attempt to remove causal agents, hyperinflammation is triggered, attracting numerous neutrophilic granulocytes, which, through the production of digestive enzymes during phagocytosis and killing, favor the production of ROS and the consequent constant release of inflammatory mediators with direct bacterial action damage on periodontal tissue. In addition, it seems that in people suffering from periodontitis, pathogen bacteria, endotoxins, and inflammatory mediators cause leucocytosis and increased lipidic metabolism, with an increase of cholesterol and hepatic triglycerides favoring the risk of CVD[78, 79]. Furthermore, a systemic increase of oxidative stress caused by periodontal disease seems to promote LDL oxidation. LDLs are cholesterol carriers with proinflammatory and pro-atherogenic activity. Periodontal treatment by scaling and root planning, and dental care instruction seem to reduce the circulating oxLDL level and, consequentially, the risk of the onset of CVD. In addition, leptin seems to be involved in bone metabolism. In recent murine studies, animals missing the leptin-codifying gene developed pronounced obesity. At the same time, mice with an adulterated leptin receptor presented overweight and T2D. Moreover, children lacking leptin showed severe obesity, but when exogenous leptin was given, obesity decreased considerably. In periodontal individuals, serum leptin seems increased[81, 82]. On the contrary, leptin in gingival fluid shows decreased levels, especially in the presence of aggressive and advanced periodontitis, advising of a protective leptin role, although this topic is still disputed.
There are no relevant data about the rate of adiponectin in gingival sulcular fluid, but in vitro it has been shown to be able to inhibit osteoclast activity induced by LPS. Thus, it seems to have anti-inflammatory and protective action against the progression of periodontitis and a predictive role for T2D.
In synthesis a recent systematic review confirmed a positive association between obesity and periodontal diseases across multiple studies and populations from around the world, but this relationship needs more investigation. The relationship appears clarified when the treatment of obesity is also analyzed. According to a recent study by Lakkis et al. some parodontopathic obese patients who underwent bariatric surgery showed weight loss and fat-mass loss after surgery, and an improvement in inflammatory conditions with the reduction of circulating markers and hyperglycemia. In addition, it seems that patients who undergo bariatric surgery show an improved response to non-surgical periodontal therapy compared with obese parodontopathic patients not treated with bariatric surgery. These data contrast with those reported by a study conducted by Zouza et al., who showed that non-surgical periodontal treatment allows a reduction of all clinical parameters of periodontal inflammation, both in obese patients and in normal-weight subjects, arguing that obesity does not negatively affect the success of periodontal therapy. Some studies also try to magnify this relationship. A recent meta-analysis indicated statistically significant associations between periodontitis and body mass index: the category of obese subjects showed an odds ratio (OR) of 1.81 the category of overweight subjects showed an OR of 1.27, and obese and overweight combined showed an OR of 2.13. Although there is insufficient evidence to provide guidelines to clinicians on the clinical management of periodontitis in overweight and obese individuals, these studies evidence a clear relationship.
Bariatric surgical procedures, including the laparoscopic adjustable gastric band (LAGB), are currently the only effective treatments for morbid obesity. The LAGB exerts its effects on satiety, reducing food intake and body weight by the modulation of both neural and hormonal responses, with the latter involving an elevation of meal-related levels of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). The brain, mainly the hypothalamus, is the organ responsible for maintaining the balance between food intake and energy expenditure by receiving peripheral signals from adipose tissue (adipose signals) and responding to them. Several neuropeptides are involved in this process, such as neuropeptide Y (NPY), which increases food consumption and decreases energy expenditure. NPY, acting through specific receptors, plays an important role in several physiological functions, including cardiovascular homeostasis and regulation of sympathetic nervous system activity. It mediates stress-induced obesity in adult male mice by activating its Y2 receptor (Y2R) in visceral adipose tissue. In fact, the expression of NPY is correlated with body weight changes, rather than with the presence of type 2 diabetes.
Chemerin is a recently identified adipokine that is highly expressed in liver and adipose tissue and is associated with adiposity, insulin resistance, MetS risk factors, and degree of nonalcoholic fatty liver. Importantly, chemerin is thought to regulate adipogenesis and metabolic homeostasis in murine and human adipocytes. Additionally, it modulates the innate immune system through its binding to the orphan G-protein coupled receptor chemokine-like receptor 1. It also modulates chemotaxis of immature dendritic cells and macrophages. Recent studies have associated chemerin with several inflammatory markers in obesity and T2D. Thus, chemerin is considered as a candidate in linking inflammation to obesity-related diseases.
Weight gain and the appearance of insulin resistance go hand in hand and are thought to be caused by an abnormal adipokine release by visceral fat. Adipocytes release retinol binding protein 4 ( RBP4) and visfatin, and their plasma levels are elevated in individuals with abdominal obesity. The observation that RBP4 induces insulin resistance by interfering with insulin receptor substrate 1 adds to the list of plasma abnormalities that link obesity with the development of T2D. At levels found in vivo these adipokines interfere with insulin receptor substrate 1 regulation (short contact) and induce its degradation (prolonged contact). Another treatment for obesity consists of behavioral weight management interventions, which consistently produce 8% to 10% reductions in body weight, although most subjects regain weight after treatment ends. One strategy for extending the effects of behavioral interventions has been the provision of extended care, which is a viable and efficacious solution to addressing the long-term maintenance of lost weight. Given the chronic disease nature of obesity, extended care may be necessary for long-term health benefits.
About the modulation of both neural and hormonal responses, periodontitis has also been associated with preterm birth. For many years, the incidence of preterm birth has not decreased in developed countries despite the promotion of public health programs. Many risk factors have been identified, including ethnicity, age, tobacco, and infection. However, the causes of almost 50% of preterm births remain unknown. As periodontal diseases are highly prevalent and negatively influence general health, worsening the incidence of CVD and diabetes, they have also been suspected to increase the rate of preterm birth. However, data on this topic remain contradictory. Physicians/obstetricians can identify women at risk of preterm birth and refer these patients to dentists for periodontal examination and treatment to limit adverse pregnancy outcomes.