Link Between Increased Satiety Gut Hormones and Reduced Food Reward After Gastric Bypass Surgery for Obesity

Abstract

Context:Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms.Objective:To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression.Design:These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies.Patients:Two groups, more than 5 months after RYGB for obesity (n = 7–11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies.Intervention:Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task.Main Outcome Measures:Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups.Results:Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1.Conclusions:Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food.

Differences in Regional Brain Responses to Food Ingestion After Roux-en-Y Gastric Bypass and the Role of Gut Peptides: A Neuroimaging Study

“…Octreotide may have a direct action on the brain (36). However, Goldstone et al (7) found no direct effect of octreotide on food reward behaviors in NW subjects or, when given with insulin, on postprandial hunger or fullness after RYGB. Insulin reduces food intake (37-39), albeit at higher concentrations, and regional differences in brain FDG uptake were found in reward regions with somatostatin with versus without low-dose insulin infusion (15), suggesting absence of basal insulin may be important.…”

“…RYGB increases their postprandial responses (2,5). The somatostatin analog octreotide inhibits gut peptide secretion, increases food intake, reduces satiety, and alters appetitive behavior after RYGB (6,7).…”

“…Two dopamine receptor radioligand PET studies, imaging only pathways using the ligand receptor, gave conflicting results (9,10). Functional MRI (fMRI) studies of responses to food cues (rather than food ingestion) have described reduced responses in regions including the dorsal striatum (reward), dorsolateral frontal cortex (DLFC) (inhibitory control), precuneus, and posterior cingulate in the fed state (11,12); and, examining predefined regions of interest in the fasted state, in the orbitofrontal cortex (OFC) and amygdala, with evidence that octreotide increases responses to food pictures in the fed state without affecting fullness (7,13). One fMRI study reported differences in response to oral glucose between lean and obese subjects in the hypothalamus, OFC, and somatosensory cortex were partially reversed after RYGB (4).…”

Integration of Sweet Taste and Metabolism Determines Carbohydrate Reward

“…Since glucose must be available in order to be metabolized, this finding provides indirect support that metabolic signals regulate brain response to calorie-predictive cues. Additional indirect evidence comes from reports that nucleus accumbens (NAcc) response to a variety of food cues is sensitive to peripheral metabolic signals associated with glucose metabolism [7–14]. …”

A resting‐state fMRI study of obese females between pre‐ and postprandial states before and after bariatric surgery

“…One important question is whether cerebral food-intake control is augmented following bariatric surgery. Several studies have examined this question, and suggested that bariatric surgery not only augments the metabolic profile of patients (Salehi & D'Alessio, 2016), but also behaviors and preferences regarding food (depending on the variation performed), with the commonly performed Roux-en-Y gastric bypass (RYGB) surgery appearing most effective in this respect, both clinically (Goldstone et al, 2015) and in animal models (Lutz & Bueter, 2016).…”