Effect of folic acid in adipocyte's DNA methylation levels in lupus patients: in vitro study

• Grant number: 22/09301-2
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): August 01, 2022
• Effective date (End): September 30, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Carolina Nicoletti Ferreira Fino
• Grantee: Letícia Lobato Souza
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/01893-2 - Progress in epigenetics on autoimmune rheumatic diseases: from basic studies to bedside in Lupus Erythematosus, Systemic, AP.JP
• Associated scholarship(s): 23/08563-6 - DNA methylation and gene expression of obesity-related genes in a culture of adipocytes, BE.EP.MS

Abstract

Systemic Lupus Erythematosus (SLE) is associated with a complex immune dysregulation and its pathophysiology involves a multifactorial interaction between several genetic, epigenetic and environmental factors. Alteration in epigenetic patterns has been proposed as an important contributing factor to the development of autoimmunity and specific phenotypic manifestations and response to treatment. It is known that the obesity epidemic has affected almost all areas of health, including the management of patients with SLE. Thus, the proposal hypothesizes that the long-term consequences of SLE alone have a major impact, but in synergy with excess adipose tissue, the burden is likely even greater and can be minimized by epigenetic modulation. Folic acid is a methyl donor for DNA methylation reactions. There is evidence that environmental stimuli, such as dietary patterns, are capable of inducing changes in DNA methylation and that folic acid supplementation can modify the DNA methylation profile. Recent evidence suggests that low folate is associated with decreased overall DNA methylation, which has been linked to an increased risk of SLE and other autoimmune diseases. Therefore, this study aims to assess a direct and mechanistic link between folic acid treatment, epigenetic patterns and inflammation in adipose tissue cells. For this, human adipose tissue will be obtained from patients with SLE and obesity. Tissues will be for secretome collection. Commercially available preadipocytes will be purchased from differentiated according to the manufacturer's instructions. The cells will be incubated with human adipose tissue secretome for 24 h at concentrations of 1% and 5%.Cells will be treated with 11.3¼M folic acid, dissolved in 1M NaOH, and a methyl donor mixture consisting of folic acid, choline chloride and vitamin B12 for 48h and exposed to vehicle control for the first 24h. Finally, RNA and DNA will be extracted for DNA methylation and gene expression analysis.