The composite alliance of FTO locus with obesity-related genetic variants

Obesity has become a genuine global pandemic due to lifestyle and environmental modifications, and is associated with chronic lethal comorbidities. Various environmental factors such as lack of physical activity due to modernization and higher intake of energy-rich diets are primary obesogenic factors in pathogenesis of obesity. Genome-wide association study has identified the crucial role of FTO (fat mass and obesity) in human obesity. A bunch of SNPs in the first intron of FTO has been identified and subsequently correlated to body mass index and body composition. Findings of in silico, in vitro, and in vivo studies have manifested the robust role of FTO in regulation of energy expenditure and food consumption. Numerous studies have highlighted the mechanistic pathways behind the concomitant functions of FTO in adipogenesis and body size. Current investigation has also revealed the link of FTO neighbouring genes i.e., RPGRIP1L, IRX3 and IRX5 and epigenetic factors with obesity phenotypes. The motive behind this review is to cite the consequences of FTO on obesity vulnerability.