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Assessment of insulin signaling and inflammatory pathways in skeletal muscle and adipose tissues of adult rats, offspring of the rats with periapical lesion

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Thaís Verônica Saori Tsosura
Total Authors: 1
Document type: Master's Dissertation
Press: Araçatuba. 2019-04-02.
Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araçatuba
Defense date:
Advisor: Doris Hissako Sumida

Fetal programming suggests that adverse stimuli applied during early fetal development can alter metabolism of the offspring, increasing the risk of disease in adulthood. Studies have shown that maternal periodontal disease in rats promotes insulin resistance (IR) in their adult offspring. However, there is a scarcity of research that investigated the relationship between maternal periapical lesion (PL) and health of offspring. PL is inflammatory process around the apex of a tooth root, caused by bacterial infection of the pulp and root canal system. This pathology is associated with increased tumor necrosis factor-alpha (TNF-α) which may stimulate inhibitor of kappa B kinase (IKK) and c-Jun amino-terminal kinase (JNK), which promote phosphorylation of substrate insulin receptor 1 (IRS-1) on serine residues, resulting in insulin signal (IS) attenuation, contributing to IR. In this context, it has become essential to investigate whether maternal PL also promotes IR in their offspring. This study aimed to investigate the effects of maternal PL in rats on plasma concentrations of glucose, insulin and TNF-α, insulin sensivity and the insulin and inflammatory signaling pathways in gastrocnemius muscle (GM) and periepididimal white adipose tissue (pWAT) of their adult offspring. Fifteen female Wistar rats (2 months old) were distributed in 3 groups: 1) control rats; 2) rats with 1 PL, which was induced in the right maxillary first molar; 3) rats with 4 PL, which were induced in the right upper and lower first and second molars. PL was induced using a surgical round bur 0.1 mm diameter. After 30 days of pulp exposure, female rats of all groups were mated with normal male rats. When the male offspring of rats of all rats reached 75 days old, the experiments were performed: 1) measures of glycemia and insulinemia, followed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), 2) analysis of plasma concentration of TNF-α by enzyme-linked immunosorbent assay method, and 3) evaluation of the pp185 tyrosine, IRS-1 serine, IKKα/β and JNK phosphorylation status in GM and pWAT by western blot method. Statistical analysis was performed by analysis of variance, followed by Tukey post hoc test (p<0.05). The results showed that maternal PL promotes in its adult offspring: 1) IR, 2) impairment in the transduction of the initial steps of IS in the GM and pWAT, 3) increased plasma concentrations of insulin and TNF-α, 4) greater IKKα/β phosphorylation status in GM and pWAT, 4) unchanged fasting glycemia; 5) no change in the JNK phosphorylation status in GM and pWAT. These results demonstrate that maternal PL is associated with IR and promotes important alterations in IS and inflammation pathways in adult offspring. This reinforces the importance that the maintenance of maternal oral health has on the general health of offspring. (AU)