GLP-1 May Modify Brain’s Response to Food

BOSTON — Gut hormone-based medications used to treat diabetes, such as glucagon-like peptide-1 (GLP-1) receptor agonists, have also been shown to reduce body weight. Now, researchers from Holland think they may, in part, know why this occurs. 

The researchers, who reported their findings at the American Diabetes Association’s 75th Scientific Sessions, said that using functional MRI (fMRI), they have been able to shed light on how GLP-1 receptor agonists alter the brain’s response to food, possibly reducing cravings and increasing satisfaction while eating.

“This is the first study to demonstrate effects of GLP-1 receptor activation on brain fMRI responses during actual food consumption and during anticipation of actual food consumption,” said Liselotte van Bloemendaal, MD, who is with VU University Medical Center in Amsterdam.

“GLP-1 receptor agonists alter consummatory and anticipatory food reward via actions on the brain, which may contribute to treatment-related weight loss.”

She and her colleagues previously demonstrated using fMRI that acute GLP-1 receptor agonist administration blunts brain responses to watching food pictures in appetite and reward-related brain areas in obese subjects and in obese patients with type 2 diabetes.

Although the viewing of food pictures is often used as a relatively simple and interesting food stimulus in fMRI studies investigating the regulation of food intake and the development of obesity, the central responses to actual food consumption may be even more important from a pathophysiological perspective, she said.

Bloemendaal and her team conducted a randomized, crossover, placebo-controlled study with obese patients with type 2 diabetes and obese normoglycemic patients and lean individuals. The cohort consisted of 48 participants.

Using fMRI, the researchers determined the acute effects of intravenous administration of the GLP-1 receptor agonist exenatide, with or without prior GLP-1 receptor blockade using exendin 9-39, on brain responses to food pictures during a somatostatin pancreatic-pituitary clamp.

The researchers found that obese patients with type 2 diabetes and obese normoglycemic subjects showed increased brain responses to food pictures in appetite-related and reward-related brain regions (insula and amygdala) compared with lean individuals. 

The study also demonstrated that exenatide decreased food intake and food-related brain responses in patients with type 2 diabetes and obese subjects in insula, amygdala, putamen and orbitofrontal cortex compared with placebo.

“Our findings demonstrate that GLP-1 receptor activation decreases anticipatory food reward, which may reduce cravings for food, and increases consummatory food reward, which may prevent overeating,” Bloemendaal told Endocrinology Advisor. 

“These insights into the central regulation of consummatory and anticipatory reward may help to develop new treatment strategies for obesity. One avenue that merits further investigation would be to study whether adding a second hormone, such as glucagon or peptide YY, to GLP-1 receptor agonist treatment could further increase weight loss.”

The researchers also found that BMI negatively correlated with brain responses to receipt of chocolate milk and positively correlated with anticipation of receipt of chocolate milk in brain areas regulating reward, appetite and motivation. 

The study demonstrated that exenatide increased brain responses to drinking chocolate milk and decreased anticipation of drinking chocolate milk compared with placebo. This was paralleled by reductions in food intake. Results also indicated that exendin 9-39 largely prevented these effects.

Bloemendaal said the researchers next plan to investigate whether GLP-1 receptor agonists also alter cravings for drugs of abuse, alcohol and nicotine. She said the findings from her group now may pave the way for a new possible therapeutic target for many substance abuse disorders.

Reference

1. van Bloemendaal L et al. Abstract 384-OR: Brain Reward-System Activation in Response to Anticipation and Consumption of Palatable Food Is Altered by GLP-1 Receptor Activation in Humans. Presented at: American Diabetes Association (ADA) 75th Scientific Sessions; June 5-9, 2015; Boston.