The efficacy of semaglutide in treating obesity may be related to its effects on taste perception and brain activity in integrative hubs beyond hypothalamic and midbrain reward circuitry, according to research presented at ENDO 2024, the Endocrine Society's annual meeting in Boston, Mass.
"Clinicians will likely correlate the findings with reports from their patients on changes in desire for certain foods, which go beyond broad changes in appetite and satiety that help them lose weight," said one of the study's investigators, Mojca Jensterle Sever, Ph.D.
The 16-week, single-blinded, randomized, placebo-controlled clinical trial, included 30 women with an average BMI of 36.4 kg/m2. Participants were randomly assigned to receive 1 mg, once weekly of semaglutide or a placebo.
Researchers measured taste sensitivity using strips containing concentrations of four basic tastes. They also used functional MRI to assess brain responses to a sweet solution dispensed on the tongue before and after the participants consumed a standard meal. Tongue biopsies were performed to evaluate mRNA expression in the collected tongue tissue.
The study revealed that women in the treatment group experienced significant changes to taste perception, taste bud gene expression, and brain activity in response to sweet taste stimuli. Genes EYA, PRMT8, CRLF1, and CYP1B1, which are associated with taste pathways, neural plasticity, and the renewal of taste buds in the tongue, exhibited differential mRNA expression in all tests conducted during the analysis.
Moreover, the study provided insights into the brain's response to the GLP-1 receptor, particularly in the angular gyrus, which influences language and number processing, memory, and reasoning. The shift in perception of reward compared to neutral feelings toward taste could have important implications for understanding and potentially modifying taste preferences in individuals with obesity.
The investigators acknowledged some limitations. "This proof-of-concept study assessed only a specific taste in a study environment, which may not reflect everyday experience. Taste perception can vary significantly from person to person, limiting the generalizability of our results. Additionally, mRNA sequencing has inherent limitations and does not directly represent changes in protein levels or activity."
Further research is needed to clarify the extent to which semaglutide's success in treating obesity is a "matter of taste."
