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

Abstract

The fat mass and obesity-associated gene (FTO) rs9939609 A-allele is associated with higher acyl-ghrelin (AG) concentrations, higher energy intake, and obesity, although exercise may mitigate rs9939609 A-allele-linked obesity risk. Butyrylcholinesterase (BChE) hydrolyzes 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. 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. Twelve AA and 12 TT normal-weight males completed a control (8 h rest) and an exercise (1 h of exercise at 70% peak oxygen uptake, 7 h rest) trial in a randomized crossover design. A fixed meal was consumed at 1.5 h and an ad libitum buffet meal at 6.5 h. Appetite, appetite-related hormones, BChE activity, and energy intake were assessed. AAs displayed lower baseline BChE activity, higher baseline AG:DAG ratio, attenuated AG suppression after a fixed meal, and higher ad libitum energy intake compared with TTs [effect sizes (ESs)≥0.72, P≤0.049]. Exercise increased Δ BChE activity in both genotypes (ESs=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 profile observed in AAs during the control trial (ESs≥1.25, P≤0.048). Exercise did not elevate energy intake in either genotype (P=0.282). 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. This trial was registered at clinicaltrials.gov as NCT03025347.