Epigenetic markers of inflammatory pathways before and after hypocaloric dietary intervention in women with grade III obesity

Author(s)

Cristiana Cortes de Oliveira

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2022-07-13

Examining board members

Carla Barbosa Nonino; Rebeca Antunes Beraldo; Gabriela Salim Ferreira de Castro; Yara Cristina de Paiva Maia

• Advisor: Carla Barbosa Nonino

Abstract

Personalized nutrition aims to provide a targeted nutritional intervention adapted to the individual\'s genome. DNA methylation changes can be dynamic due to environmental stimuli or they can be stable and passed on to the next generations. Epigenetic marks can be modified and the understanding of the factors involved in these changes can be crucial for the prevention and/or treatment of diseases. The aim of the present study was to identify changes in the DNA methylation pattern involved with inflammation pathways after hypocaloric dietary intervention in women with grade III obesity and to compare them with women with normal weight. This was a longitudinal study, in which were collected anthropometric measurements of weight, height, body mass index (BMI) and waist circumference (WC), body composition (lean body mass (MCM) and fat mass (MG)) by electrical bioimpedance and DNA methylation analysis. There was a significant decrease in weight, BMI, lean body mass and fat mass after dietary intervention. When comparing the two study groups, there was a significant difference for the indicators of weight, BMI, CA, MCM and MG, both in the moment before and after dietary intervention. It was found that 16,064 CpGs sites had their methylation levels modified after dietary intervention, with 1,324 CpG sites being different between patients with obesity before the intervention and women with normal weight and, after the dietary intervention, 78,596 CpGs sites were different. Of the total CpGs that modified methylation levels after dietary intervention, 19 were in genes related to inflammation pathways, with 9 CpGs having their methylation levels reduced and 10 CpGs increased. Positive correlations were observed between the levels of DNA methylation of CpGs in the CCL24, NFKB2 and RIPK2 genes before the dietary intervention with the percentage of weight loss and with the variations in the total cholesterol, AST and ALT concentrations after dietary intervention. Multiple linear regression analysis showed contribution of methylation levels of cg25634545 in the NFKB2 gene just before the intervention in the variation of total cholesterol concentrations with dietary intervention, even after adjusted for age, weight loss (%) and loss of MG. We conclude that the hypocaloric dietary intervention provides weight loss, reduction of anthropometric measures and is capable of altering the DNA methylation levels of genes related to the inflammatory pathways, showing a decrease in the methylation of genes involved with the increase of the inflammation process. (AU)

• FAPESP's process: 16/06470-7 - Identification of genetic markers associated with metabolic answers after diet hypocaloric intervention in women with obesity level III
• Grantee: Cristiana Cortes de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate