Untargeted and targeted gingival metabolome in rodents reveal metabolic links between high-fat diet-induced obesity and periodontitis.

AIM: To characterize gingival metabolome in high-fat diet (HFD)-induced obesity in mice with/without periodontitis. METHODS: HFD-induced obesity mouse model was established by 16-week feeding, and a lean control group was fed with low-fat diet (n = 21/group). Both models were induced for periodontitis on the left sides by molar ligation for 10 days, whereas the right sides were used as controls. Gingival metabolome and arginine metabolism were analysed by non-targeted/targeted liquid chromatography-mass spectrometry. RESULTS: Of 2247 reference features, presence of periodontitis altered 165 in lean versus 885 in HFD mice; and HFD altered 525 in absence versus 1435 in presence of periodontitis. Compared with healthy condition, periodontitis and HFD had distinct effects on gingival metabolome. Metabolomic impacts of periodontitis were generally greater in HFD mice versus lean controls. K-medoids clustering showed that HFD amplified the impacts of periodontitis on gingival metabolome in both intensity and extensity. Ten metabolic pathways were enriched, including 2 specific to periodontitis, 5 specific to HFD and 3 shared ones. Targeted validation on arginine metabolism confirmed the additive effects between HFD and periodontitis. CONCLUSION: The obese population consuming excessive HFD display amplified metabolic response to periodontitis, presenting a metabolic susceptibility to exacerbated periodontal destruction.

Hyperuricemia as a potential plausible risk factor for periodontitis.

Elevated blood uric acid (UA) levels have been positively associated with the severity of periodontitis. It thus brings out a hypothesis that hyperuricemia, a pathological elevation of blood UA, might be a risk factor for periodontitis. Namely, periodontitis individuals with Hu might acquire more severe periodontal destruction compared to those without Hu. To support the hypothesis, four aspects of evidences are proposed. First, hyperuricemia and periodontitis share many metabolic and inflammatory comorbidities such as metabolic syndrome, diabetes and cardiovascular diseases which are commonly related to elevated UA levels and gout. Second, observational and interventional studies have found altered UA levels in blood and saliva in periodontitis patients or after periodontal treatment, suggesting an epidemiological connection between hyperuricemia and periodontitis. Third, plausible immuno-metabolic mechanisms by which hyperuricemia might promote the progression of periodontitis are suggested, such as impaired immune response, oxidative stress, pathological bone remodeling and dysbiosis. The last, our empirical data exhibited elevated UA levels in gingival tissue in periodontitis mice compared to controls. If the hypothesis is true, given the high prevalence of the two conditions, hyperuricemia would be a significant risk factor increasing the global burden of periodontal diseases. Evidences on a directional correlation between hyperuricemia and periodontitis are sparse. Longitudinal and experimental studies would be necessary to determine the magnitude of periodontal risk, if any, exacerbated by hyperuricemia and the underlying mechanisms.

[Long-term high-fat diet inhibits hippocampal expression of insulin receptor substrates and accelerates cognitive deterioration in obese rats].

OBJECTIVE: To assess the effect of long-term high-fat diet on the expressions of insulin receptor substrates in the hippocampus and spatial learning and memory ability of obese rats. METHODS: A total of 100 4-week-old male SD rats were randomly divided into two groups and fed with common diet (CD group, n=40) or high-fat diet (HFD group, n=60) for 16 weeks. At 4, 8, 12, 16 and 20 weeks, 8 rats were randomly selected from each group for testing their spatial learning and memory function using Morris water maze. After the tests, the rats were sacrificed for measurement of the metabolic parameters and detection of the expressions of insulin receptor substrate-1 (IRS-1) and IRS-2 mRNAs in the CA1 region of the hippocampus. RESULTS: Compared with those in CD group, the rats in HFD group showed a prolonged escape latency, longer swimming distance, faster average swimming speed, and shorter stay in the platformat 12 weeks. In HFD group, the serum levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and fasting insulin were all significantly increased (P<0.05) and the level of high-density lipoprotein cholesterol decreased (P<0.01) in comparison with those in CD group at each of the time points. No significant difference was found in fast glucose levels between the two groups (P>0.05), but the expressions of IRS-1 and IRS-2 mRNAs were significantly decreased in HFD group at 12 weeks (P<0.05). CONCLUSION: In obese rats, long-term feeding with high-fat diet leads to insulin resistance, which interferes with hippocampal expression of insulin receptor substrates and insulin metabolism to cause impairment of the cognitive function and accelerate cognitive deterioration.