Epigenomic regulation of fat patterning in women (apple vs. pear)

• Grant number: 18/17711-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): July 01, 2019
• Effective date (End): June 30, 2020
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Ellen Cristini de Freitas
• Grantee: Flávia Giolo de Carvalho
• Supervisor: Lauren Sparks
• Host Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Translational Research Institute for Metabolism and Diabetes (TRI), United States
• Associated to the scholarship: 17/08036-5 - Effects of taurine supplementation associated or not to exercise on mitochondrial function, energy expenditure and inflammatory profile in obese women, BP.PD

Abstract

Since that obesity is associated with disturbs in fat cell gene expression and metabolism, understanding how obesity metabolism and what strategies could reduce its impact provides an important clinical challenge. Our global hypothesis is that cell autonomous differences in adipocytes are epigenetically driven and critical to our understanding of the risk for metabolic diseases development in both men and women. Aims: Compare genome-wide differences in epigenetic marks in abdominal vs gluteal subcutaneous adipose tissue and adipocytes. This epigenetic pattern will be defined first in healthy pear-shape women, then we will compare pear-shape and apple-shape women and finally between women and men. Methods: This is a prospective, cohort study to address epigenetic mechanisms underlying differences in the regulation of adipose tissue distribution in men and women. Twenty seven subjects will be enrolled during this study. The study will consist of three groups of subjects determined by sex, body max index (BMI) and fat distribution: Group A Women - Healthy 'pears' - will consist of healthy women with a BMI between 23 and 35 kg/m2 as a waist-to-hip ratio of 0.78 or less; Group B Women - Healthy 'apples' - will consist of healthy women with a BMI between 23 and 35 kg/m2 as a waist-to-hip ratio of 0.85 or more; Group C Men - Healthy 'apples' - will consist of men with a BMI between 23 and 35 kg/m2. There will be a first screening phase and then subjects will undergo baseline testing (Visit 1) including blood analysis and detailed body composition by DEXA. During the next visit and an overnight fast (Visit 2), adipose tissue biopsies will be performed. On a subsequent day (Visit 3), after an overnight fast, two intravenous will be inserted for routine blood samples (free fat acids, insulin, glucose, C-peptide, adiponectin and archive samples) followed by frequently sampled intravenous glucose tolerance testing (FSIVGTT). During the FSIVGTT, the indirect calorimetry (RMR/RQ) will be used as a measure of metabolic flexibility. Regarding adipose tissue, the RNA will be extracted from ~200mg of adipose tissue through a sequential extraction procedure using TriZol, and will be sent for RNA-sequencing or ready to reverse transcriptase; and adipose tissue explants (100mg) will be incubated for proteins secretion analyses using a multiplexed immunoassay platform (Meso Scale Discovery) and or proteomics. Immunohistochemistry will be performed in order to identify adipocytes and macrophages. The adipose cell size will be determined by microscope analysis. All data will be entered into the Translational Research Institute for Metabolism and Diabetes (TRI-MD) clinical research database (iDiscover) and analyzed with Statistical Analysis System (SAS). (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 CARVALHO, FLAVIA G.; JUSTICE, JAMIE N.; DE FREITAS, ELLEN C.; KERSHAW, ERIN E.; SPARKS, LAUREN M.. Adipose Tissue Quality in Aging: How Structural and Functional Aspects of Adipose Tissue Impact Skeletal Muscle Quality. NUTRIENTS, v. 11, n. 11, NOV 2019. (17/08036-5, 18/17711-0)