Metabolic mechanisms of the fat mass and obesity-associated (FTO) gene

The modern obesogenic lifestyle encompasses an environment that promotes weight gain in the form of body fat accumulation. Genetic variations can predispose some individuals to be more susceptible to developing obesity in a similar environment (Hainer et al. 2000; Maes et al. 1997; Mustelin et al. 2009). As the prevalence of obesity increases worldwide, and becomes a substantial socioeconomic issue, the need for research that deepens our understanding of the underlying genetic influences on complex regulatory mechanisms governing energy homeostasis becomes increasingly necessary. The fat mass and obesity-associated (FTO) gene has been strongly linked to an increased obesity risk through numerous genome wide association (GWA) studies over the past decade. However, information regarding FTO’s peripheral influences, specifically on skeletal muscle metabolism, is limited. The broad aim of this dissertation was to identify metabolic differences between risk allele and non-risk variants of FTO, and to determine the impact of physical stress (in the form of exercise) on FTO expression and function. Thus, the experiments presented in this dissertation were designed to investigate whether differences across genotype alleles of the FTO rs9939609 (T>A) polymorphism existed for metabolic flexibility in response to a nutritional challenge, and for metabolic profiles, FTO expression and FTO function in skeletal muscle following acute exercise stimuli