一项随机交叉试验评估了肥胖相关 FTO rs9939609 多态性变异的正常体重男性急性运动对食欲、循环 ghrelin 浓度和丁酰胆碱酯酶活性的影响。

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.

机构信息

National Centre for Sport and Exercise Medicine, School of Sport, Exercise, and Health Sciences, Loughborough University, Loughborough, United Kingdom.

Ingestive Behavior Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.

出版信息

Am J Clin Nutr. 2019 Nov 1;110(5):1055-1066. doi: 10.1093/ajcn/nqz188.

DOI:10.1093/ajcn/nqz188

PMID:31504106

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, 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.

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 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.

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 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).

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. This trial was registered at clinicaltrials.gov as NCT03025347.

摘要

背景

脂肪量和肥胖相关基因（FTO）rs9939609A 等位基因与较高的酰基-ghrelin（AG）浓度、较高的能量摄入和肥胖有关，尽管运动可能会减轻 rs9939609A 等位基因相关的肥胖风险。丁酰胆碱酯酶（BChE）将 AG 水解为去酰基-ghrelin（DAG），可能会降低食欲。然而，FTO rs9939609 基因型和运动对 BChE 活性、AG、DAG 和能量摄入的影响尚不清楚。

目的

我们假设肥胖风险 A 等位基因（AA）纯合子个体的餐后 AG 和能量摄入会高于低肥胖风险 T 等位基因（TT）纯合子个体，但运动可以增加 BChE 活性并减少这些差异。

方法

12 名 AA 和 12 名 TT 正常体重男性以随机交叉设计完成对照（8 小时休息）和运动（70%最大摄氧量运动 1 小时，7 小时休息）试验。在 1.5 小时时摄入固定餐，在 6.5 小时时摄入自助餐。评估食欲、食欲相关激素、BChE 活性和能量摄入。

结果

AA 组基线 BChE 活性较低，基线 AG:DAG 比值较高，固定餐后 AG 抑制作用减弱，自由饮食时能量摄入较高（效应大小（ES）≥0.72，P≤0.049）。运动增加了两种基因型的ΔBChE 活性（ES=0.37，P=0.004）；然而，运动使 AA 组的 AG 和 AG:DAG 比值降低幅度更大（P≤0.023），抵消了 AA 组在对照试验中观察到的较高的 AG 谱（ES≥1.25，P≤0.048）。运动并没有增加两种基因型的能量摄入（P=0.282）。