Chronic semaglutide alters ingestive behavior without impairing taste function in mice

Area of Science:

• Neuroscience
• Metabolic Disorders
• Sensory Science

Background:

• Glucagon-like peptide-1 receptor (GLP-1R) agonists, including semaglutide, are effective obesity treatments.
• The precise mechanisms by which GLP-1R agonists reduce food intake are not fully understood.
• Conflicting results exist regarding the impact of GLP-1R agonists on taste function.

Purpose of the Study:

• To systematically investigate the effects of chronic semaglutide treatment on taste responsivity in diet-induced obese mice.
• To determine if semaglutide alters responses to sweet, bitter, sour, salty, and fatty tastants.
• To assess the impact of semaglutide on sweet taste sensitivity and behavioral engagement.

Main Methods:

• Diet-induced obese mice received chronic semaglutide treatment or vehicle.
• Brief-access gustometer tests were used to evaluate taste responses.
• Psychophysical analysis assessed sucrose concentration-response functions and EC50 values.
• Histological analysis examined taste receptor cell subtypes and gene expression.

Main Results:

• Semaglutide induced significant weight loss but did not alter lick rates for any tastant.
• Sweet taste sensitivity (EC50) remained unchanged, indicating intact peripheral taste function.
• Semaglutide increased licking and trial initiation for sucrose, suggesting enhanced behavioral engagement.
• No changes were observed in taste receptor cell subtypes or taste signaling gene expression.

Conclusions:

• Chronic semaglutide treatment does not impair peripheral taste function in obese mice.
• GLP-1R agonists likely influence ingestive behavior via mechanisms independent of taste signaling.
• Potential mechanisms involve alterations in motivational processes rather than taste perception.