Sex-specific brain atlas of GLP-1 reveals why weight-loss drugs may work differently

Researchers map the peptide behind semaglutide across 25 brain regions in each sex, finding striking differences in appetite and reward circuits.

Published on Mar. 10, 2026

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A new peer-reviewed study has constructed the first comprehensive sex-specific atlas of GLP-1 expression in the murine brain, identifying the peptide across 25 distinct brain nuclei, subnuclei, and regions in each sex. The findings reveal that the geography of GLP-1 in the brain is not uniform between females and males, with striking differences in appetite and reward circuits that may explain why GLP-1 analogs used to treat obesity work differently in women and men.

Why it matters

Obesity and diabetes are common in both women and men, yet certain pathological and psychiatric features of these conditions exhibit sex-specific differences. This atlas provides critical insights into how GLP-1, a key regulator of appetite and metabolism, is expressed differently in the female and male brain, which could inform the development of more effective and personalized GLP-1-based therapies.

The details

Researchers at the Icahn School of Medicine at Mount Sinai employed an advanced RNA detection technique called RNAscope to map Glp1 expression across the entire mouse brain in three female and three male animals. They found notable sex differences, including higher Glp1 densities in the female medulla and male olfactory bulb. Several medullary nuclei displayed sex-biased expression, with Glp1 transcripts detected only in certain regions of females or males. The olfactory bulb, which is implicated in appetite regulation, showed significantly greater Glp1 density in the granular cell layer of males compared to females.

  • The research was published on March 10, 2026.

The players

Vitaly Ryu

Co-first author and lead designer of the experiments.

Mone Zaidi

Senior author and Institute Director at the Icahn School of Medicine at Mount Sinai.

Anisa Gumerova

Co-first author.

Georgii Pevnev

Co-author.

Tony Yuen

Co-author.

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What they’re saying

“What struck us was not just where we found GLP-1 expression, but the degree to which the pattern diverged between females and males in specific hindbrain subnuclei. Several medullary nuclei displayed expression in only one sex, which opens entirely new questions about how GLP-1 circuits operate differently in the female and male brain.”

— Vitaly Ryu, Co-first author (Brain Medicine)

“The implications extend well beyond metabolism. With growing evidence that GLP-1 analogs may help prevent or treat cognitive decline, and given that we can detect Glp1 transcripts in Alzheimer's-vulnerable regions in the mouse brain, this atlas should help guide future investigations into how GLP-1 acts on neuroinflammation, neuronal degeneration, and memory loss.”

— Mone Zaidi, Senior author and Institute Director, Icahn School of Medicine at Mount Sinai (Brain Medicine)

What’s next

The researchers note that the relatively small sample size of three animals per sex limits statistical power, particularly for detecting low-abundance or regionally sparse Glp1-expressing cells. Future studies with larger sample sizes could provide additional insights into the sex-specific expression patterns of GLP-1 in the brain.

The takeaway

This comprehensive atlas of GLP-1 expression in the female and male mouse brain provides critical insights into the neuroanatomical basis for the sex-specific effects of GLP-1 analogs on appetite, metabolism, and potentially other psychiatric and cognitive functions. These findings could guide the development of more personalized and effective GLP-1-based therapies for obesity, diabetes, and other brain-related disorders.