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

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Dorling, J.L., Clayton, D.J. ORCID: 0000-0001-5481-0891, Jones, J., Carter, W.G., Thackray, A.E., King, J.A., Pucci, A., Batterham, R.L. and Stensel, D.J., 2019. 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. The American Journal of Clinical Nutrition, 110 (5), pp. 1055-1066. ISSN 0002-9165

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Official URL: http://doi.org/10.1093/ajcn/nqz188

Abstract

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 ab 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 ≥ 0.76, P ≤ 0.049). Exercise increased delta BChE activity in both genotypes (ES = 0.41, P = 0.004); however, exercise lowered AG and the AG/DAG ratio to a greater extent in AAs (P ≤ 0.041), offsetting the higher AG ghrelin profile observed in AAs during the control trial (ES ≥ 0.88, 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.

Item Type:

Journal article

Alternative Title:

Ghrelin, exercise and FTO rs9939609 genotype [short running title]

Publication Title:

The American Journal of Clinical Nutrition

Creators:

Dorling, J.L., Clayton, D.J., Jones, J., Carter, W.G., Thackray, A.E., King, J.A., Pucci, A., Batterham, R.L. and Stensel, D.J.

Publisher:

Oxford University Press

Date:

November 2019