Endocrine Abstracts

Background: Obese individuals may perceive the taste of caloric dense food as less intense, resulting in decreased activation of the reward system. Preclinical research provides some insights into the role of GLP-1 in the gustatory coding. The impact of GLP-1 receptor agonists on the tongue and taste perception remains largely unaddressed in clinical settings.

Aim: to investigate the impact of semaglutide on the tongue transcriptome, taste perception and brain response to visual food cues and sweet tasting solution.

Methods: Thirty obese women with polycystic ovary syndrome (age 33.7 ± 6.1 years, BMI 36.4 ± 4.4 kg/m², mean ± SD) were randomized to once weekly semaglutide (SEMA) 1.0 mg s.c. or placebo in a 16-week, single-blind, placebo-controlled study. Participants underwent the biopsies of the tongue. Transcriptomic profile of tongue tissue was assessed as changes in expression level measured by RNA sequencing (NovaSEQ 6000 sequencer, Illumina). Taste sensitivity was evaluated by chemical gustometry using a validated examination method consisting of 16 taste strips including 4 different concentrations of sweet, sour, salty and bitter. The change in neural response to visual food cues and to sweet-tasting solution was assessed by functional MRI. In the first task, subjects were shown a series of calorie-dense, calorie-low food and non-food cues. In the second task, the neural responses to the tasting of sweet solution dripped on the tongue was assessed. Both tasks were performed in fasting state and repeated after the meal ingestion. Change in eating behaviour was evaluated by the Three-Factor Eating Questionnaire (TFEQ-R18).

Results: A total of 1326 genes were differentially expressed in the tongue tissue between the SEMA and placebo with log FC>0.7 or <.7 and FDR<0.05. Gene ontology analysis identified altered pathways in WNT signalling, fat cell differentiation, reproductive regulation and carbohydrate and fatty acid metabolism. Semaglutide improved taste sensitivity for all four basic tastes. The ability to resist emotional eating improved in SEMA group. Furthermore, semaglutide decreased activation in response to food pictures in the right putamen after the meal (P<0.001) and increased activation in response to sweet solution in the region of angular gyrus (P<0.001).

Conclusion: Semaglutide modified transcriptomic profile in the tongue along with improved taste perception. Furthermore, it decreased activation in putamen in response to high caloric food cues and increased activation of angular gyrus in response to sweet tasting solution. This implies an impact of semaglutide on gustatory coding up to brain integrative centres.