2134/38361 James L. Dorling James L. Dorling David J. Clayton David J. Clayton Jenny Jones Jenny Jones Wayne Carter Wayne Carter Alice Thackray Alice Thackray James King James King Andrea Pucci Andrea Pucci Rachel L. Batterham Rachel L. Batterham David Stensel David Stensel A randomized crossover trial assessing the effects of acute exercise on appetite, circulating ghrelin concentrations, and butyrylcholinesterase activity in normal-weight males with variants of the obesity-linked FTO rs9939609 polymorphism Loughborough University 2019 Exercise Ghrelin Appetite FTO gene Butyrylcholinesterase Obesity Medical and Health Sciences not elsewhere classified 2019-07-19 08:31:36 Journal contribution https://repository.lboro.ac.uk/articles/journal_contribution/A_randomized_crossover_trial_assessing_the_effects_of_acute_exercise_on_appetite_circulating_ghrelin_concentrations_and_butyrylcholinesterase_activity_in_normal-weight_males_with_variants_of_the_obesity-linked_FTO_rs9939609_polymorphism/9614363 Background: The fat mass and obesity-associated gene (FTO) rs9939609 A-allele is associated with higher acyl-ghrelin (AG) concentrations, higher energy intake and obesity, though exercise may mitigate rs9939609 A-allele linked obesity risk. Butyrylcholinesterase (BChE) hydrolyses AG to des-acyl-ghrelin (DAG), potentially decreasing appetite. However, the effects of the FTO rs9939609 genotype and exercise on BChE activity, AG, DAG and energy intake are unknown. Objective: We hypothesized that individuals homozygous for the obesity-risk A-allele (AAs) would exhibit higher postprandial AG and energy intake than individuals homozygous for the low obesity-risk T-allele (TTs), but that exercise would increase BChE activity and diminish these differences. Methods: Twelve AA and 12 TT normal weight males completed a control (8 hours rest) and an exercise (1 hour of exercise at 70% peak oxygen uptake, 7 hours rest) trial in a randomized cross-over design. A fixed meal was consumed at 1.5 hours and an ad libitum buffet meal at 6.5 hours. Appetite, appetite-related hormones, BChE activity and energy intake were assessed. Results: AAs displayed lower baseline BChE activity, higher baseline AG/DAG ratio, attenuated AG suppression after a fixed meal and higher ad libitum energy intake than TTs (ES ≥ 0.72, P ≤ 0.049). Exercise increased delta BChE activity in both genotypes (ES = 0.37, P = 0.004); however, exercise lowered AG and the AG/DAG ratio to a greater extent in AAs (P ≤ 0.023), offsetting the higher AG ghrelin profile observed in AAs during the control trial (ES ≥ 1.25, P ≤ 0.048). Exercise did not elevate energy intake in either genotype (P = 0.282). Conclusions: Exercise increases BChE activity, suppresses AG and the AG/DAG ratio and corrects the higher AG profile observed in obesity-risk AA individuals. These findings suggest that exercise or other methods targeting BChE activity may offer a preventative and/or therapeutic strategy for AA individuals.