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

Abstract

The phenomenon known as programming suggests that stimuli, applied during early fetal development, may alter metabolism of offspring, increasing the risk of disease in adulthood. Studies have demonstrated that adult rats, offspring of rats with periodontal disease (PD) present several pathological alterations, such as insulin resistance (IR), a major characteristic of type 2 diabetes. However, studies investigating the effects of maternal periapical lesion (PL) on offspring health are scarce. PL is characterized as an inflammation at the apex of the dental root usually caused by infection by bacteria from the root canal system. This pathology is associated with increased proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), that can stimulate serine kinases, including IkB kinase (IKK) and c-Jun amino-terminal kinase (JNK), which attenuate the insulin signaling contributing to IR. In this context, is fundamental to investigate whether maternal PL also promotes IR in its offspring, as observed in maternal PD. In view of this, the objectives of this study will be to evaluate in adult rats, offspring of rats with PL: 1) glycemia; 2) insulinemia; 3) insulin sensitivity; 4) plasma concentration of TNF-alpha; 5) pp185 (IRS-1/IRS-2) tyrosine phosphorylation status in gastrocnemius muscle (GM), periepididymal white adipose tissue (WAT); 6) IRS-1 serine phosphorylation status in GM and WAT; 7) IRS-1 content in GM and WAT; 8) JNK and IKKalpha/beta phosphorylation status in GM and WAT; 9) JNK and IKKalpha/beta content in GM and WAT. For this purpose, female Wistar rats (2 months of age) will be distributed into three groups: 1) control rats (CN); 2) group with one PL induced in the upper right first molar (PL1); 3) group with four PLs induced in the first and second upper and lower right molars (PL4). PL will be induced using a carbon steel drill with a ball at the end with 0.1 mm. After 30 days of pulp exposure, the rats of all groups will be placed for mating. Pregnant rats will be separated into individual cages. When male offspring of all rats completet 75 days, the experiments will be performed. Statistical analysis will be performed by analysis of variance (ANOVA), followed by the Tukey test. The level of significance adopted will be 5%. (AU)