Abstract
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.
Highlights
Genetic variations can predispose some individuals to be more susceptible to weight gain and obesity in the modern obesogenic environment [1,2]
Of particular interest has been the fat mass and obesity-associated (FTO) gene, with those homozygous for A-allele demonstrating an association with body mass index (BMI), waist circumference, type 2 diabetes (T2D), and other obesity-related traits [3,4,5]
Participants were excluded from participating if they had diagnosed diabetes, were performing any regular fitness training (>30 min, 3 × per week) for 6 months prior, were taking contraindicated prescription medication that influenced their metabolism or were pregnant
Summary
Genetic variations can predispose some individuals to be more susceptible to weight gain and obesity in the modern obesogenic environment [1,2]. While the mechanisms behind these associations are yet to be established, one reason could be due to higher food intake and diminished food satiety [6,7,8], with several lines of evidence supporting FTO’s role in regulating energy intake and eating behaviour [9,10]. A gut “hunger hormone”, is a key mediator of appetite and subsequent body weight regulation. Recent evidence suggests that perturbations to circulating ghrelin levels and neural responses to food cues could explain FTO’s association with increased susceptibility to gaining weight.
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