Effects of gut hormones, glucagon-like peptide-1 and desacyl ghrelin, on eating behaviour in obesity and ex-smokers

Abstract

Introduction: Unhealthy eating behaviour is more prevalent in obesity and contributes to weight regain after dieting. Smoking cessation weight gain, a common reason for relapse to cigarettes, also has adverse health consequences. Gut hormones, such as GLP-1 and desacyl ghrelin (DAG), reduce appetite and weight in obesity and Prader-Willi syndrome. GLP-1 and ghrelin signalling systems modulate central reward networks for food and nicotine in preclinical and human studies. However, the impact of GLP-1 and DAG on neurocircuitry involved in eating behaviour in obesity and ex-smokers remains unclear therefore further insight is needed to guide clinical use of gut hormones in prevention of weight gain during dieting and smoking cessation.

Aims: Here, the effects of acute administration of GLP-1 analogue, Exenatide or DAG was explored in dieting adults with obesity, or in abstinent nicotine-dependence (double blind randomised placebo controlled cross-over design), on food cue responsivity using fMRI in reward-processing regions, food intake, food reward and appetite.

Results: In dieting group with obesity, both Exenatide and DAG increased BOLD signal to high-energy (HE) food pictures in prefrontal cortex regions, implicated in inhibitory control. In contrast, in ex-smokers, both Exenatide and DAG decreased BOLD signal to HE food pictures in the mesolimbic reward-processing regions and prefrontal cortex, suggesting a reduction in anticipatory food reward with a concomitant decrease in executive control. With Exenatide, there was also a reduction in HE food appeal, food intake and appetite ratings in both groups. With DAG, there was no overall effect on HE food appeal, food intake or appetite ratings in both groups.

Conclusion: These findings are in accord with the possibility that Exenatide and DAG could be used in prevention of smoking cessation weight gain. This experimental medicine study has provided pilot data for a larger clinical study to trial these gut hormones as potential therapies in smoking cessation.