Cholecystokinin and gut-brain signalling.

Area of Science:

• Neuroscience
• Gastroenterology
• Endocrinology

Background:

• Enteroendocrine cells monitor gut contents, influencing digestion and food intake via hormones.
• Vagal afferent neurons are key targets for gut hormones controlling appetite.
• The intestinal hormone cholecystokinin (CCK) plays a crucial role in this communication.

Purpose of the Study:

• To investigate how CCK influences the neurochemical phenotype of vagal afferent neurons.
• To understand CCK's role in encoding nutrient ingestion status.
• To elucidate CCK's gatekeeper function in appetite and satiety signaling.

Main Methods:

• Analysis of gene and receptor expression in vagal afferent neurons under varying CCK conditions (fasting vs. post-prandial).
• Assessment of neurochemical changes, including cannabinoid CB1, MCH-1, Y2 receptors, MCH, and CART expression.
• Correlation of these neurochemical changes with appetite and satiety signaling capacities.

Main Results:

• Low CCK (fasting) upregulates appetite-stimulating receptors (CB1, MCH-1) and neuropeptide (MCH) while downregulating satiety peptide (CART).
• High CCK (post-prandial) downregulates CB1 and MCH-1 but upregulates Y2 receptors and CART, while decreasing MCH.
• These changes alter vagal afferent neuron signaling capacity, promoting appetite or satiety.

Conclusions:

• CCK's presence or absence dictates the neurochemical state of vagal afferent neurons.
• This neurochemical encoding determines the neuron's capacity for appetite stimulation or satiety signaling.
• CCK acts as a critical gatekeeper, modulating vagal afferent neuron responses to other signals.