Aim To investigate the plasma concentrations of glucose, insulin and tumour necrosis factor‐α (TNF‐α) of rats with maternal apical periodontitis (AP) and to explore the effect of maternal inflammation on the initial steps of insulin signalling and the inflammatory pathway in the gastrocnemius muscle (GM) and periepididymal white adipose tissue (pWAT) of adult offspring. Methodology Fifteen female Wistar rats were distributed into a control group (CN), a group with 1 tooth with AP (1AP) and a group with 4 teeth with AP (4AP). Thirty days following induction of AP, female rats from all groups were mated with healthy male rats. When male offspring reached 75 days of age, plasma concentrations of glucose, insulin and TNF‐α were quantified. Insulin resistance was evaluated by the homoeostasis model assessment of insulin resistance (HOMA‐IR) index. Phosphorylation status of pp185 tyrosine, insulin receptor substrate 1 (IRS‐1) serine, IκB kinase α/β (IKKα/β) and c‐Jun N‐terminal kinase (JNK) in the GM and pWAT were measured by Western blot. Analysis of variance was performed, followed by the Tukey's post hoc test. P values <0.05 were considered to be statistically significant. Results Maternal AP promoted insulin resistance, impaired the initial steps of insulin signalling, significantly increased plasma concentrations of insulin (P < 0.001) and TNF‐α (P < 0.05), and enhanced IKKα/β phosphorylation in the GM and pWAT (P < 0.05) of adult offspring. However, maternal AP did not affect fasting glycaemia and JNK phosphorylation in the GM and pWAT of adult offspring. Conclusions Maternal AP was associated with insulin resistance in adult offspring through alterations in insulin signalling and inflammation pathways. The study provides information on the impact of maternal AP on the development of metabolic alterations such as insulin resistance in adult offspring and reinforces the importance of preventing maternal AP in order to maintain the general health of offspring.

PLs promoted an increase in macrophage infiltration, activation of inflammatory pathways in muscle tissue, and serum concentrations of HSP70 and LPS in rats. The present study improves the knowledge on the impact of oral inflammations on the development of systemic alteration, which can induce insulin resistance.

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Background Maternal periodontal disease leads to low birth weight (LBW), insulin resistance (IR), increased TNF‐α levels, and alterations in insulin signaling in adult offspring. TNF‐α has been associated with the stimulation of IKKβ/NF‐κB, resulting in the decreased expression of GLUT4. Another mechanism that may be involved in decreasing GLUT4 expression is DNA methylation. This study aimed to evaluate in the adult offspring of rats with periodontal disease: IR, inflammatory pathways, DNA methylation, and expression of GLUT4. Methods Female Wistar rats were distributed into control and experimental periodontal disease groups. Seven days after induction of periodontal disease, both groups were mated with healthy male rats. After weaning, male offspring were distributed into control offspring (CN‐o) and periodontal disease offspring (PED‐o) groups. Body weights were measured from 0–75 days of age. At day 75, the following were measured in the offspring: IR (HOMA‐IR index); TNF‐α and NF‐κBp65 content in the gastrocnemius muscle (GM) by western blotting; IKKα/β, JNK, ERK 1/2, NF‐κBp65, and NF‐κBp50 phosphorylation status in the GM by western blotting; DNA methylation by restriction digest and real‐time PCR(qAMP); and expression of GLUT4 mRNA in the GM by real‐time PCR. Results LBW, IR, increases in TNF‐α, IKKα/β, ERK 1/2, NF‐κBp65, and NF‐κBp50 decreased expression of GLUT4 mRNA were observed in the PED‐o rats. No differences were identified in JNK phosphorylation status and DNA methylation in the evaluated regions of the GLUT4‐encoding gene Slc2a4. Conclusion Maternal periodontal disease causes LBW, IR, activation of inflammatory pathways, and decreased GLUT4 expression in the GM of adult offspring.

Aim To verify the effects of melatonin supplementation on insulin sensitivity, plasma concentrations of inflammatory cytokines, insulin signalling and inflammatory pathways in the soleus (SM) and extensor digitorum longus (EDL) muscles of rats with apical periodontitis (AP). Methodology Seventy‐two Wistar rats were distributed into 4 groups: (a) control (C), (b) control supplemented with melatonin (M), (c) AP (AP), and (d) AP supplemented with melatonin (AP + M). AP was induced by pulp exposure of the maxillary and mandibular right first and second molars to the oral environment. After AP induction, oral supplementation with 5 mg kg−1 melatonin (diluted in drinking water) for 60 days was initiated. At the end of the treatment, the following were analysed: (1) plasma concentrations of insulin and inflammatory cytokines (TNF‐α, IL‐6, IL‐1β and IL‐10) using ELISA kits; (2) glycaemia using enzymatic assay; (3) insulin resistance using homoeostasis model assessment of insulin resistance (HOMA‐IR) index; and (4) phosphorylation status of pp185 tyrosine, Akt serine, IKKα/β, and JNK in SM and EDL using Western blot. Analysis of variance of two or three factors was performed, followed by the Bonferroni test. P values < 0.05 were considered statistically significant. Results AP promoted insulin resistance, significantly increased (P < 0.05) plasma concentrations of pro‐inflammatory cytokines (TNF‐α, IL‐6, and IL‐1β), significantly decreased (P < 0.05) the concentration of anti‐inflammatory cytokine IL‐10, impaired insulin signalling in SM, and increased IKKα/β phosphorylation status in SM and EDL. Melatonin supplementation in rats with AP improved insulin sensitivity, significantly decreased (P < 0.05) TNF‐α and IL‐1β, significantly increased (P < 0.05) IL‐10 plasma concentrations, and changed the insulin signalling in soleus muscle and IKKα/β phosphorylation status in SM and EDL muscles. Conclusions Melatonin is a potent adjuvant treatment for improving apical periodontitis‐associated changes in insulin sensitivity, insulin signalling and inflammatory pathways. In addition, the negative impact of AP on general health was also demonstrated.

Fluoride is an essential trace element for the maintenance of bone health owing to its capacity to stimulate proliferation and osteoblastic activity that can lead to increased bone formation. However, excessive sodium fluoride (NaF) intake can impair carbohydrate metabolism thereby promoting hyperglycemia, insulin resistance, and changes in insulin signaling. Thus, this study aimed to evaluate the effect of chronic treatment with NaF in bone metabolism, insulin signaling, and plasma concentrations of glucose, insulin, tumor necrosis factor-α (TNF-α), osteocalcin (OCN), and fluoride in ovariectomized rats. Thirty-two ovariectomized Wistar rats were randomly distributed into two groups: Control (OVX-C) and those undergoing treatment with NaF (50mg F/L) in drinking water for 42days (OVX-F). Glucose and insulin levels were assessed, followed by homeostasis model assessment of insulin resistance (HOMA-IR). Akt serine phosphorylation was evaluated by western blotting. Plasma concentrations of TNF-α and OCN were evaluated by ELISA. The left and right tibia was collected for immunohistochemical and histomorphometric analysis, respectively. Chronic treatment with NaF promoted insulin resistance, decreased insulin signal, increased plasma concentration of insulin, fluoride, OCN and TNF-α, decreased trabecular bone area of the tibia, and caused changes in bone metabolism markers in ovariectomized rats. These results suggest the need for caution in the use of NaF for the treatment of osteoporosis, especially in postmenopausal woman.

The present study indicates that preventing endodontic disease can thwart insulin resistance.

Highlights Periapical lesions promotes higher T-bet expression and lower GATA3 and FOXP3 expression. Periapical lesion promotes increased GATA3 and decreased FOXP3 expression in the group with 4 periapical lesions (4PL) The adaptive immune system, with a predominance of the Th1 polarization, may be involved in the development of insulin resistance in rats with Periapical lesions.