Postdoctoral Fellow Khalifa University, United Arab Emirates
Abstract: Obesity remains a pressing public health issue in the Gulf region including UAE, with studies identifying a strong association between the FTO gene variant rs9939609 and increased obesity risk. Individuals with the A/A genotype are more prone to obesity, while those with the T/T genotype are more likely to maintain a healthy weight. The FTO gene encodes an m6A RNA demethylase, which regulates key RNA metabolic processes involved in adipogenesis. While human studies on FTO function yield mixed results, animal models consistently show that FTO deficiency leads to reduced body weight, whereas overexpression results in increased adiposity. This study aims to examine the role of FTO genetic variants in adipogenesis, using induced pluripotent stem cells (iPSCs) derived from individuals with the A/A and T/T genotypes. These iPSCs will be differentiated into adipocytes, including brown and beige subtypes, to explore the impact of FTO-related m6A modifications on adipocyte function. To broaden the scope of our analysis, we will also investigate additional obesity-linked FTO variants, such as rs1421085 and rs8050136, known to influence thermogenesis and adipose tissue gene expression. Finally, we will evaluate the effects of small molecules that modulate FTO activity to better understand their potential to influence adipogenesis and restore metabolic balance. By integrating genetic, molecular, and pharmacological approaches, this research study aims to uncover the mechanisms linking FTO genetic variants to obesity and identify potential therapeutic targets for metabolic disorders.
