Obesity, defined as abnormal or excessive fat accumulation that increases the risk of chronic disease, has been increasingly linked with periodontal disease. Reports show that individuals who become obese have a higher risk of developing periodontal disease (relative risk (RR) = 1.33, 95% confidence interval (CI) = 1.21–1.47) compared with counterparts of normal weight [1
]. Obese individuals have also been shown to have a significantly higher risk of experiencing periodontal disease progression than individuals with normal weight after adjusting for important co-factors (RR = 1.36, 95% CI = 1.04–1.78) [2
]. These observations indicate that obesity is a risk for periodontal disease.
Obesity is associated with a systemic increase in reactive oxygen species (ROS) production [3
]. Although ROS are products of normal cellular metabolism, overproduction of ROS induces oxidative stress by damaging DNA, lipids, and protein [5
]. Oxidative stress plays a crucial role in the pathogenesis of a number of diseases, including periodontal disease [6
]. In vitro studies have shown that oxidative stress stimulates osteoclast differentiation [7
]. Animal studies have also suggested that oxidative stress is involved in the progression of alveolar bone resorption [9
]. In a recent review, the basis for the relationship between obesity and periodontitis lies at a fundamental intracellular level, which includes oxidative stress [13
]. Thus, gingival oxidative stress due to obesity may induce the progression of periodontal disease through increased alveolar bone resorption.
Molecular hydrogen is an antioxidant that can reduce oxidative stress [14
], and drinking hydrogen-rich water (HW) can increase the concentration of molecular hydrogen in blood and tissues [15
]. In dentistry, animal studies have demonstrated that HW can reduce gingival oxidative stress following aging [16
] and periodontal disease [17
]. A recent study also revealed that drinking HW activated the gene expression of antioxidant defense, contributing to an acceleration of oral mucosal wound healing in rats [18
]. These studies used rats with normal weight. Therefore, the antioxidative effect of HW may offer clinical benefits even in obese rats by limiting obesity-induced oxidative stress. However, it is unclear how HW affects gingival oxidative stress and alveolar bone resorption resulting from obesity.
In the present study, we hypothesized that drinking HW might prevent gingival oxidative stress and alveolar bone resorption in obesity. 8-Hydroxydeoxyguanosine (8-OHdG), which is formed when the guanine in DNA undergoes oxidative damage, is generally accepted as a reliable indicator of oxidative stress [19
]. In addition, feeding test subjects a high-fat diet is one of the useful experimental models to investigate periodontal disease progression in obesity [20
]. The purpose of the present study was to investigate the effects of HW on gingival 8-OHdG levels and alveolar bone resorption in obese rats fed a high-fat diet.
In the present study, the rats on a high-fat diet, compared with the control rats, showed increased body weight gain and higher levels of serum and gingival 8-OHdG at 20 weeks. 8-OHdG is an indicator of oxidative stress [18
]. These findings indicate that, in the obese rats, a high-fat diet induced a systemic increase in oxidative stress. On the other hand, drinking HW suppressed the effects of a high-fat diet on body weight gain, and showed lower levels of serum and gingival 8-OHdG compared with the obese rats. It is feasible that HW suppresses obesity, which in turn might inhibit a systemic increase in oxidative stress, including gingival oxidative stress.
Some studies have investigated the anti-oxidative effects of HW in obesity. For instance, one animal study has revealed that drinking HW reduced obesity and reduced hepatic oxidative stress in a mice model [26
]. A clinical study also showed that consumption of HW decreased the level of urinary lipid peroxidation significantly from baseline to Week 8 in obese subjects [27
]. These are consistent with our findings, which exhibited that drinking HW prevented obesity and gingival oxidative stress.
In our findings, the obese rats on a high-fat diet showed a greater distance between the CEJ-ABC, a lower BT/TV, and a higher Tb. Sp than the control rats, suggesting that the progression of alveolar bone resorption follows obesity. The results also revealed that the rats fed a high-fat diet and HW, compared with the HFD rats showed a lower distance between the CEJ-ABC and a greater BT/TV. Gingival oxidative stress is involved in the progression of alveolar bone resorption [11
]. Suppression of obesity by drinking HW may attenuate alveolar bone resorption by limiting gingival oxidative stress.
This study exhibited that drinking HW upregulated the gene expression of Sod2 and Sod3 in gingival tissues. Sod2 and Sod3 are antioxidant enzymes that catalyze the conversion of superoxide radicals into hydrogen peroxide and oxygen [28
]. This suggests that the increased antioxidative properties of gingival tissues by HW might also protect periodontal tissues from a systemic increase in oxidative stress.
The present results also showed that HW downregulated the gene expression of Fancc. Since Fancc is considered an oxidative stress responsive gene [30
], and it is suggested that the downregulation of Fancc reflected decreased gingival oxidative stress.
It is reported that drinking HW can improve cholesterol metabolism [27
], which may have a direct influence on bone resorption [31
]. However, in our findings, there were no significant differences in serum cholesterol and triglyceride between the rats with and without HW intake. These suggest that gingival oxidative stress and alveolar bone resorption were not related to serum cholesterol and triglyceride in our animal model.
In this study, the rats on a high-fat diet tended to exhibit lower levels of total and VLDL triglycerides in serum compared to the control rats. These findings are similar to those of the previous study in birds on a high-fat diet [32
]. The reduced serum triglyceride concentrations may reflect a possible metabolic overcompensation in response to the added dietary fat [33
A clinical study showed that obesity may influence periodontal tissue destruction and disease severity by increasing the level of oxidative stress in the presence of periodontal disease [34
]. Another study also suggested that periodontal oxidative stress generated by obesity seems to be associated with periodontal disease [35
]. Such evidence supports the concept that obesity may lead to the progression of periodontal disease by increasing oxidative stress. On the other hand, the present report showed that drinking HW suppressed obesity, gingival oxidative stress, and alveolar bone resorption in rat models. Our previous study also found that exercise training prevented obesity and gingival oxidative stress in rats on a high-fat diet [22
]. Anti-obesity therapy to reduce oxidative stress may be useful in preventing periodontal disease related to obesity.
In our previous study, broccoli supplementation inhibited the effects of a high-cholesterol diet on osteoclast differentiation in the periodontal tissue [36
]. It is also reported that supplementation of coenzyme 10 counteracted the negative effects of n-6 polyunsaturated fatty acid on age-related alveolar bone loss [37
]. Furthermore, the present study demonstrated that drinking HW attenuates alveolar bone resorption related to obesity. Action of adequate nutrient consumption would be important to maintain and/or improve periodontal health.
When taking medicine, it is necessary to be careful about side effects. However, HW has no known side effects in previous animal and human studies [16
]. Therefore, HW may constitute useful preventive treatment against periodontal disease related to obesity without side effects.
Our study has some limitations. For instance, no data were collected with regard to the circulating inflammatory molecules, such as tumor necrosis factor-α. Obesity could indirectly result in an increase in the circulation of inflammatory molecules that could augment the inflammation induced by bacterial pathogens. In addition, while we showed preventive effects of HW on obesity and gingival oxidative stress, we could not fully elucidate the relationship between these pathological mechanisms and the effects of HW. Further studies are needed to clarify this point.