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

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.