Results from epidemiological studies suggest that there is an association between periodontitis and prediabetes, however, causality is not known. The results from our previous studies suggest that induction of periodontitis leads to hyperinsulinemia glucose intolerance and insulin resistance, all hallmarks of prediabetes. However, global effects of periodontitis on critical organs in terms of metabolic alterations are unknown.
We determined the metabolic effects of periodontitis on brain, liver, heart and plasma resulting from Porphyromonas gingivalis induced periodontitis in mice. Periodontitis was induced by oral application of the periodontal pathogen, Porphyromonas gingivalis for 22 weeks. Global untargeted biochemical profiles in samples from these organs/plasma were determined by liquid and gas chromatography/mass spectrometry and compared between controls and animals with periodontitis.
Oral application of Porphyromonas gingivalis induced chronic periodontitis and hallmarks of prediabetes. The results of sample analyses indicated a number of changes in metabolic readouts, including changes in metabolites related to glucose and arginine metabolism, inflammation and redox homeostasis. Changes in biochemicals suggested subtle systemic effects related to periodontal disease, with increases in markers of inflammation and oxidative stress most prominent in the liver. Signs of changes in redox homeostasis were also seen in the brain and heart. Elevated bile acids in liver were suggestive of increased biosynthesis, which may reflect changes in liver function. Interestingly, signs of decreasing glucose availability were seen in the brain. In all three organs and plasma, there was a significant increase in the microbiome-derived bioactive metabolite 4-ethylphenylsulfate sulfate in animals with periodontitis.
The results of metabolic profiling suggest that periodontitis/bacterial products alter metabolomic signatures of brain, heart, liver, and plasma in the prediabetic state. These data provide scientific community valuable metabolic signatures that become the basis for understanding the impact of periodontitis on a systemic disease and potentially targets for therapeutic intervention.
Cadmium is an environmental toxin strongly associated with the development of cancer, kidney and liver disease, and bone demineralization. Whether cadmium causes obesity in humans remains a subject of controversy in the literature. An NHANES study that examined the effect of various toxic metals on central obesity demonstrated a decrease in the BMI of subjects exposed to cadmium. The purpose of this study is to examine the effect of cadmium on visceral adipose tissue (VAT), the potential for chelation to reverse cadmium‐induced changes, and to investigate the mechanism by which these changes occur. VAT is the subset of adipose tissue most heavily implicated in the pathogenesis of obesity, insulin resistance, and metabolic syndrome. ICR mice were placed into one of three groups: control, cadmium followed by washout, and cadmium followed by chelation. Mice in the two experimental groups were treated with 100ppm CdCl2 drinking water for 8 weeks followed by either 8 weeks of washout or 8 weeks of chelation with DMSA. Digital analysis of H&E images was performed using ImageJ and morphometric parameters of approximately 400 adipocytes per group were obtained. A 14.6% reduction in adipocyte size was observed in the group treated with cadmium followed by washout relative to the control group (p < 0.0001). In the group that underwent chelation after cadmium exposure, there was an increase in adipocyte size relative to the cadmium‐washout group (p<0.002). Additionally, animals in the cadmium‐washout group had a 5% reduction in body weight relative to control (p<0.0001). There was no significant difference in weight between the control group and the cadmium‐chelation group. In conclusion, the mouse model we have developed demonstrates that chronic low dose cadmium exposure causes weight loss and that chelation has the potential to reverse this change. Although the effect of cadmium on body weight remains controversial, this mouse model may serve to clarify this relationship and address the mechanism of cadmium’s action.
Support or Funding Information
NIEHS Grant # P30 ES027792‐02
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