Epigenetic effects of high fat diet in adipose tissue of animals with lupus

• Grant number: 21/09753-8
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): February 01, 2022
• Effective date (End): February 29, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Carolina Nicoletti Ferreira Fino
• Grantee: Amanda Alves Ribeiro
• 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): 22/13266-8 - IL-2 gene expression in adipocytes from lupus patients in different nutritional status: in vitro study, 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 and epigenetic factors. Changes in epigenetic patterns have been proposed as an important contributing factor to the development of autoimmunity and phenotypic manifestations and response to treatment. The study aims to investigate whether the IL-2 / IL-17A / Stat3/ CREM2 pathway is epigenetically altered in an animal model of SLE on a standard high-fat diet and to investigate whether the supplementation of methyl donors (folic acid and vitamin B12) reverses or minimizes these possible abnormalities in obese and non-obese animals. About 40 NZBWF1/J female mice (approximate weight 200 g and age 8 weeks) will be randomized into two groups. For eight weeks, one group (CONTROL GROUP; n = 20) will receive a regular chow (STD; commercial diet AIN-93, ~ 4.2 kcal/g) and the other (OBESITY GROUP; n = 20) will be fed one high-fat diet (HFD; ~6.6 kcal/g) aiming at weight gain. After this period, the animals will receive supplementation of folic acid + vitamin B12 (8 mg of folic acid + 50 µg vitamin B12 per kg of feed) for another eight weeks. At the end of the experiment, the animals will be anesthetized and sacrificed and samples of blood, adipose tissue (white and brown, liver and pancreas) will be collected. Biological samples will be used for epigenetic analysis (DNA methylation, hydroxymethylation and microRNA) and gene expression . In the statistical analyzes the Shapiro-Wilk test, independent t test, Mann-Whitney U test will be used, Repeated measures ANOVA and/or Wilcoxon tests. Interactions will be inferred through linear regressions and Pearson or Spearman correlation. Data analysis will be performed using the Statistical Package for Social Science (SPSS version 22.0 Inc. Chicago. IL). The level of significance will be set at p d 0.05.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RIBEIRO, Amanda Alves. Epigenetic effects of a high-calorie, high-fat diet and micronutrient supplementation in animals with lupus. 2024. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.