Interaction of circulating GLP-1 and the response of the dorsolateral prefrontal cortex to food-cues predicts body weight development

Abstract

ObjectivesThis study evaluated the impact of the interaction between the anorexigenic incretin hormone glucagon-like peptide-1 (GLP-1) and reward-related brain activity in the dorsolateral prefrontal cortex (DLPFC), a key area of behavioral control, on future weight loss in obese individuals.MethodsWe performed a weight loss-weight maintenance intervention study over 27 months. We applied an fMRI food-cue reactivity paradigm during which the participants were passively exposed to food pictures to evaluate neuronal activity in the DLPFC. Additionally, we measured concentrations of circulating GLP-1 levels during a standard oral glucose tolerance test. Phenotyping was performed consecutively before and after a 3-month low-calorie diet as well as after a randomized 12-month trial, investigating the effect of a combined behavioral intervention on body weight maintenance. Participants were then followed-up for another 12 months without further intervention.ResultsUsing voxel-wise linear mixed-effects regression analyses, we evaluated 56 measurements and identified a strong interaction between circulating, endogenous GLP-1 levels and DLPFC activity predicting body weight change over the total observation period (t = −6.17, p = 1.6 · 10−7). While neither the GLP-1 nor the DLPFC response individually predicted the subsequent weight change, participants achieved body weight loss when the GLP-1 and the DLPFC responses occurred concurrently.ConclusionsOur data demonstrate an interaction between a peripheral hormonal signal and central nervous activity as robust predictor of body weight change throughout the different periods of a long-term life-style intervention. The preeminent role of their interdependency compared to the partly ambivalent effects of the single components argues for integrative approaches to improve sensitivity and reliability of weight prediction conventionally based on individual biomarkers.

Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward

“…In the opposing direction, endogenous circulating concentrations of GLP-1 following consumption of a sugary beverage are negatively associated with dorsal striatum and OFC activation upon visual food cue presentation [ 25 , 26 ]. Further, in overweight participants following a weight loss program, postprandial GLP-1 levels along with dorsolateral prefrontal cortex (PFC) responsiveness to food cues were the best predictors of body mass index reduction [ 27 ]. Thus, interventions targeting food cue reactivity via GLP-1 signaling could be of interest for therapies targeting obesity.…”

Obesity and Dietary Added Sugar Interact to Affect Postprandial GLP-1 and Its Relationship to Striatal Responses to Food Cues and Feeding Behavior

“…Activation of GLP-1 receptors using GLP-1 analogues decreases drug reward and striatal c-fos expression in mice ( 10 ). In humans, neuroimaging studies in humans have found that infusions of GLP-1 ( 11 ) and GLP-1 agonists ( 12 ), or glucose-induced GLP-1 increases ( 13 , 14 ) alter brain responses to food cues in regions of the brain involved in the regulation of eating. A previous study from our laboratory ( 15 ) found a negative correlation between GLP-1 response to oral glucose and activation of the dorsal striatum in response to high-calorie food images, relative to nonfood images, in lean young adults.…”

Modulation of Short-Chain Fatty Acids as Potential Therapy Method for Type 2 Diabetes Mellitus

“…GLP-1 is an anorexigenic incretin hormone that enhances glucose-dependent insulin secretion [ 66 ]. The interaction between circulating levels of GLP-1 and food reward-related central nervous activity in the dorsolateral prefrontal cortex can achieve body weight loss in obese individuals [ 67 ]. PYY is costored and cosecreted with GLP-1 by enteroendocrine-L cells [ 35 ].…”