New Insights into the Effect of Gut Hormones on the Brain

Peptide hormones from the gut bind to specific receptors in the brain. As a result, these hormones influence food intake and metabolism. The role of these peptide receptors in critical developmental phases is still poorly understood. Scientists at the DZD partner German Institute of Human Nutrition (DIfE) have now studied the expression patterns of key receptors in the hypothalamus of mice. The results have been published in the journal 'PLOS One'.

[Translate to Englisch:] Übertragen von Hirnschnitten der Maus mit einem Pinsel auf einen Objektträger. © David Ausserhofer/DIfE

The hypothalamus is an important brain region that controls metabolism. Changes in maternal nutrition during development affect the hypothalamus, but the underlying mechanisms are still poorly understood.

The team led by Dr. Rachel Lippert, head of the junior research group Neural Circuits at DIfE, has investigated three main receptors for gut hormones and their role in the hypothalamus during the first weeks of life in a mouse model. This phase corresponds to the last trimester of pregnancy in humans in terms of brain development.

The receptors GIPR, GLP1R and CCK2R play important roles in glucose regulation, food intake and energy balance. They could be potential targets for the treatment of obesity and diabetes.

The study highlights the interactions between gut hormones and brain development. The results could provide insights into the effects of maternal nutrition on the offspring and help develop treatment strategies for metabolic disorders.

The junior research group Neural Circuits led by Dr. Rachel Lippert (front center). © Susann Ruprecht/DIfE


Background information on the three receptors
The gastric inhibitory polypeptide receptor (GIPR) is expressed in pancreas, stomach, heart, kidney, liver, adipose tissue and brain. It functions as a signal mediator in the gut-brain axis. While activation of the receptor in the pancreas stimulates insulin release, in the brain it causes reduced food intake and weight loss.

The glucagon-like peptide-1 receptor (GLP1R) is expressed in the pancreas, lung, stomach, heart, kidney and brain. It is involved in the control of blood glucose levels by stimulating insulin release in the pancreas. Activation of the receptor in the hypothalamus results in reduced food intake.

The cholecystokinin receptor 2 (CCK2R) is highly expressed in the brain, particularly in the hypothalamus. It functions as a signal mediator in the gut-brain axis and is involved in digestion, emotions and memory regulation.

Original publication:
Cantacorps, L., Coull, B. M., Falck, J., Ritter, K., Lippert, R. N.: Gut-derived peptide hormone receptor expression in the developing mouse hypothalamus. PLoS One 18(8):e0290043 (2023). [Open Access] 


Detailed information in the DIfE press release