There is evidence from pre-clinical studies that food intake and appetitive gut hormones, including ghrelin and glucagon-like peptide-1 (GLP-1), not only alter appetite, but also food and non-food reward processing, as well as addictive behaviours influencing eating behaviour. There is more limited evidence from human studies. This talk will review our human studies using multi-modal phenotyping, including functional MRI, to study the food-gut-brain axis in eating and addictive behaviours.

Using a platform of experimental medicine outcome measures including functional MRI paradigms with a food picture evaluation task (to assess cue reactivity or anticipatory reward) [Goldstone AP et al. Eur J Neurosci 2009; Scholtz S et al. Gut 2014; Goldstone AP et al. AJCN 2014; Goldstone AP et al. JCEM 2016], we have studied the effects of food intake, acute administration of orexigenic hormone acyl ghrelin, and comparison of Roux-en-Y gastric bypass (RYGB) with gastric banding surgery for obesity, and acute pharmacological suppression of satiety gut hormones post-bariatric surgery, on eating behaviour and food cue reactivity. Our more recent studies have examined (i) the longitudinal effects of RYGB surgery, endoscopic insertion of the duodenal-jenunal bypass liner (Endobarrier) device for obesity and diabetes (compared with standard medical management), (ii) in our Gut Hormone in Addiction (GHADD) study, the effects of acute infusion of the GLP-1 analogue, Exenatide, in obesity, ex-smokers or abstinent alcohol dependence, and (iii) differences in eating and addictive behaviours in adults with obesity with vs. without binge eating symptoms, while (iv) ongoing studies are examining the role of the recently identified endogenous anorexigenic liver/intestinal hormone LEAP2 that is an inverse agonist at the ghrelin GHSR receptor.

Changes in appetite and food cue reactivity with fasting or after food intake appear contributed to by reciprocal changes in gut hormones such as acyl ghrelin and LEAP2. Reduced food cue reactivity and motivation for food after RYGB surgery appears related to post-surgical exaggerated satiety gut hormones PYY and GLP-1 responses. Our results also indicate: (i) a potential for GLP-1 analogues in preventing smoking cessation weight gain, (ii) enhanced wanting and liking of high fat food, impaired non-food related motor response inhibition (impulsivity) and alterations in negative emotional reactivity in adults with vs. without binge eating symptoms, and (iii) a stimulatory effect of GHSR signalling on striatal high-energy vs. low-energy food cue reactivity, that is attenuated by LEAP2 acting as a satiety hormone.