Effect of maternal periodontal disease in DNA methylation of GLUT4 and IRS-1 in skeletal muscle tissue of adult offspring

• Grant number: 17/12405-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2017
• End date: August 31, 2019
• Field of knowledge: Health Sciences - Dentistry - Social and Preventive Dentistry
• Principal Investigator: Doris Hissako Matsushita
• Grantee: Bianca Elvira Belardi
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

The fetal programming hypothesis suggests that intrauterine stimuli or aggression can induce metabolic and physiology changes in offspring, increasing the diseases risk in adulthood. Permanent changes in DNA methylation and gene expression are considered molecular mechanisms responsible for this programming. Previous studies have shown that maternal periodontal disease (PD) promotes insulin resistance, increased in the plasma concentrations of cytokines, decrease in GLUT4 content in the plasma membrane and its translocation index in their adult offspring. Cytokines such as TNF-± have been associated with reduced GLUT4 expression. Moreover, this cytokine may stimulate some serine kinases including IºB kinase (IKK), c-Jun N-terminal protein kinase (JNK), which promote IRS-1 phosphorylation on serine residues, resulting in attenuation of the insulin signal. These findings reveal the need for more studies to verify the mechanisms involved in these changes. Therefore, the objectives of the present study will be evaluate in adult rats, offspring of rats with periodontal disease: 1) plasma concentrations of glucose and insulin; 2) the degree of DNA methylation in the promoter region of gene of GLUT4 and IRS-1 in gastrocnemius skeletal muscle tissue (GM). The rats will be distributed into two groups: 1) with periodontal disease (PED), in which the disease is induced by ligation with silk thread around the 1st molar, 2) control rats (CN). Seven days after ligature placement, the rats of both groups will be placed for mating, verifying daily by vaginal smear, the day of copulation. Pregnant rats will be separated into individual boxes. When male offspring of these rats completed 75 days, will be performing the experiments: 1) plasma concentrations of glucose and insulin; 2) the degree of DNA methylation in the promoter region of gene of GLUT4 and IRS-1 in GM. Statistical analysis will be done by T Student method for unpaired samples, and the differences between the two groups will be considered significant when p <0.05. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE LIMA COUTINHO MATTERA, MARIA SARA; CHIBA, FERNANDO YAMAMOTO; LOPES, FLAVIA LOMBARDI; SAORI TSOSURA, THAIS VERONICA; PERES, MARIA ANGELICA; BALERA BRITO, VICTOR GUSTAVO; PENHA DE OLIVEIRA, SANDRA HELENA; PEREIRA, RENATO FELIPE; MARANI, FERNANDO; DOS SANTOS, RODRIGO MARTINS; et al. Effect of maternal periodontitis on GLUT4 and inflammatory pathway in adult offspring. Journal of Periodontology, v. 90, n. 8, p. 884-893, AUG 2019. (15/12018-7, 17/12405-6)