Assessment of obesity-mediated epigenetic modification of DNA damage repair genes

Financed by: The Bureau of Educational and Cultural Affairs of the U.S. Department of State

Programme: Fulbright U.S. Postdoctoral Scholar

Grant agreement ID: JR-2021

Duration: October 2021 to June 2022

Beneficiary: Pallavi Kompella

Supervisor: Manuel Macías González

Implementation centre: Virgen de la Victoria University Hospital

Research group of IBIMA involved: Obesity, Diabetes and their Comorbidities: Prevention and Treatment

ABSTRACT

Several studies suggest the role of epigenetics in causing obesity. Only recently have we begun to understand that obesity can elicit epigenetic modifications. Studies show that a higher body mass index (BMI>25 kg/m²) is associated with the methylation of genes involved in lipid metabolism and inflammation. In women with obesity, hypermethylation of specific genes in mammary and endometrial cells increases the risk of breast and endometrial cancer. In various cancers, the epigenetic modification of DNA damage repair (DDR) genes can impact DDR protein activity, leading to inefficient repair. Accumulation of damages in DNA can then cause increased errors during DNA synthesis, resulting in genomic instability. A recent study showed a marked increase in DNA damage and decreased DDR efficiency in various tissues from obese mice compared to normal-weight mice. However, how obesity impacts the expression and methylation pattern of DDR genes in humans is not well established. Therefore, we are studying the obesity-mediated expression and epigenetic modification of DDR genes, focusing on 8-oxoguanine DNA glycosylase (OGG1) involved in the base excision repair (BER) pathway.