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EVALUATION OF THE GLOBAL EXPRESSION OF MYRNAS IN WHITE ADIPOSE TISSUE IN ADULT RATS, OFFSPRING OF RATS WITH PERIODONTAL DISEASE

Grant number: 23/03786-7
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2023
Effective date (End): May 31, 2024
Field of knowledge:Health Sciences - Dentistry - Social and Preventive Dentistry
Principal Investigator:Doris Hissako Matsushita
Grantee:Gabriele Fernandes Baliero
Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

The fetal programming hypothesis suggests that stimuli or aggression during intrauterine life may result in permanent alterations in the physiology and metabolism of the offspring, increasing the risk of diseases in adult life. Changes in miRNA expression patterns are considered molecular mechanisms responsible for this programming. Previous studies have shown that maternal periodontal disease (PD) promotes insulin resistance, increased plasma concentrations of cytokines, reduced GLUT4 content, its rate of translocation to the plasma membrane, and its expression in adult offspring. Furthermore, maternal periodontal disease was able to activate inflammatory pathways in the skeletal muscle tissue of the adult offspring, this activation was proven by the increased expression of TNF-±, NF-kBp65, NF-kBp50, IKKa/b and ERK1/2. However, there was no change in GLUT4 gene DNA methylation and JNK expression in adult offspring. Through these results, it was possible to infer that one of the reasons for the reduction of GLUT4 expression in the muscle tissue of adult rats offspring of rats with PD was due to the activation of inflammatory pathways. Furthermore, according to the postdoctoral project of co-advisor Maria Sara, 11 miRNAs were modulated in adult rats offspring of rats with periodontal disease (fold change ± 1.5; p <0.05) when compared to control rats in muscle tissue skeletal. Among these 5 miRNAs were upregulated (miR-3556b; miR-3544; miR-181d; miR-223-3p; miR-211-3p) and 6 downregulated (miR-126a-3p; miR-101a-3p; miR-499b -5; miR-146-5p; miR-182; miR-465-5p) (unpublished data). Such findings highlight the need for further studies to verify whether other tissue, such as adipose tissue, presents alterations in the global expression of microRNA in adult offspring. Therefore, the objectives of the present study will be to evaluate in adult rats, offspring of rats with periodontal disease: a) to analyze the global expression of miRNAs in periepididymal white adipose tissue (WAT); b) Western Blotting to validate the pathways that miRNAs act. The rats will be divided into two groups: 1) with periodontal disease (PD), in which this disease will be induced by ligation with silk thread around the 1st lower molar; 2) control rats (CN). After 7 days of placement of the ligature, the rats of both groups will be placed for mating, verifying daily, by vaginal smear, the day of copulation. When the male offspring of these rats are 75 days old, the experiments will be carried out: analysis of the global expression of miRNAs (by the microarray technique) in WAT.

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