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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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posted on 19.07.2019, 08:31 by James L. Dorling, David J. Clayton, Jenny Jones, Wayne Carter, Alice ThackrayAlice Thackray, James KingJames King, Andrea Pucci, Rachel L. Batterham, David StenselDavid Stensel
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.

Funding

This research was supported by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, the Rosetrees Trust, Stoneygate Trust, Robert Luff Foundation and an NIHR Research Professorship to Rachel L Batterham

History

School

  • Sport, Exercise and Health Sciences

Published in

The American Journal of Clinical Nutrition

Volume

110

Issue

5

Pages

1055 - 1066

Citation

DORLING, J.L. ... et al., 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.

Publisher

Oxford University Press (OUP)

Version

AM (Accepted Manuscript)

Rights holder

© American Society for Nutrition

Publisher statement

This is a pre-copyedited, author-produced version of an article accepted for publication in The American Journal of Clinical Nutrition following peer review. The version of record James L Dorling, David J Clayton, Jenny Jones, Wayne G Carter, Alice E Thackray, James A King, Andrea Pucci, Rachel L Batterham, David J 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, The American Journal of Clinical Nutrition, 110 (5), pp.1055-1066, is available online at: https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqz188/5554776 and https://doi.org/10.1093/ajcn/nqz188.

Acceptance date

18/07/2019

Publication date

2019-08-26

Copyright date

2019

ISSN

0002-9165

eISSN

1938-3207

Language

en