Researchers discover how GLP-2 receptor suppresses hunger and food intake

Researchers have discovered how a hormone in the gut slows the rate at which the stomach empties and thus suppresses hunger and food intake. Results of the animal study will be presented Monday at The Endocrine Society's 94th Annual Meeting in Houston.

"The gut hormone glucagon-like peptide 2, or GLP-2, functions as a neurotransmitter and fine-tunes gastric emptying through-as suspected-its receptor action in the brain," said the lead investigator, Xinfu Guan, PhD, assistant professor of pediatrics and medicine at Baylor College of Medicine in Houston.

The researchers found that this action occurs in the GLP-2 receptor specifically in a key group of nerve cells in the brain, called pro-opiomelanocortin, or POMC, neurons. These neurons are in the hypothalamus, the part of the brain that produces appetite-controlling neuropeptides.

In their study using molecular methods, mice lacking this GLP-2 receptor in the POMC neurons showed late-onset obesity and higher food intake compared with normal wild-type mice. The mutant, or GLP-2 receptor "knockout," mice also had accelerated gastric emptying after a liquid meal, as found on a noninvasive breath test. The faster the gastric emptying, the higher the food intake, scientists know.

Therefore, obese people may have something wrong with this hormone receptor, which alters their gastric emptying rate, Guan speculated. Many studies have shown that nondiabetic, obese humans have accelerated gastric emptying.

The researchers also found that this receptor quickly activated the PI3K intracellular signaling pathway in the POMC neurons. This, in turn, induces neuronal excitation (transmission of signals) and gene expression, according to Guan.

These findings, Guan said, show that in the central nervous system the GLP-2 receptor plays an important physiological role in the control of food intake and gastric emptying.

"This study has advanced our understanding of the brain-gut neural circuits that mediate eating behavior via modulating gastric emptying, which contributes to the control of body weight," he said.