Revealing a new brain circuit for satiety

2024

Challenge

Anti-obesity medications like semaglutide have been prescribed to roughly one out of every eight American adults to treat obesity, a chronic disease linked to increased risk of type 2 diabetes, cardiovascular disease, and many other health problems. Such medications suppress appetite by activating cellular receptors called glucagon-like peptide-1 (GLP-1) receptors. However, despite their widespread use, researchers do not have a clear understanding of how they act in the body, including how they influence groups of brain cells that influence complex behaviors like eating by working together in neural ‘circuits.’

Advance

IRP researchers created a detailed map of a neural circuit that leads to appetite suppression and weight loss in response to chemicals that activate GLP-1 receptors, generally known as GLP-1 receptor agonists. The specific neural circuit they identified resides in the brain’s hypothalamus, a part of the brain that regulates many bodily functions, including hunger and thirst. The study utilized a new technique developed by the IRP scientists, which both identifies neurons that communicate with one another and provides a list of the genes that are active — or ‘expressed’ — in those neurons.

Impact

By uncovering previously unknown neurons that are sensitive to GLP-1 receptor agonists, the study points to neural circuits that can now be studied further to develop additional obesity treatments that may have fewer side effects. The study also demonstrates a new, widely applicable technique researchers can use to explore how anti-obesity medications affect neurons.

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