Similarities in Metabolic Flexibility and Hunger Hormone Ghrelin Exist between FTO Gene Variants in Response to an Acute Dietary Challenge

The rs9939609 polymorphism of the fat mass and obesity-associated (FTO) gene has been associated with obesity, and studies have also shown that environmental/lifestyle interaction such as dietary intake might mediate this effect. The current study investigates the postprandial hormonal regulators of hunger and indirect markers of substrate utilisation and metabolic flexibility following a dietary challenge to determine if suppression of circulating ghrelin levels and/or reduced metabolic flexibility exist between FTO genotypes. One hundred and forty seven healthy, sedentary males and females (29.0 ± 0.7 yrs; 70.2 ± 1.1 kg; 169.1 ± 0.8 cm; 24.5 ± 0.3 kg/m²) complete a single experimental session. Anthropometric measures, circulating levels of active ghrelin, insulin and glucose, and substrate oxidation via indirect calorimetry, are measured pre-prandial and/or post-prandial. The FTO rs9939609 variant is genotyped using a real-time polymerase chain reaction. Metabolic flexibility (∆RER) is similar between FTO genotypes of the rs9939609 (T > A) polymorphism (p > 0.05). No differences in pre-prandial and/or postprandial substrate oxidation, plasma glucose, serum insulin or ghrelin are observed between genotypes (p > 0.05). These observations are independent of body mass index and gender. Altered postprandial responses in hunger hormones and metabolic flexibility may not be a mechanism by which FTO is associated with higher BMI and obesity in healthy, normal-weighted individuals.