"The study, led by Lisa Beutler, MD, PhD, assistant professor of Medicine in the Division of Endocrinology, Metabolism and Molecular Medicine, improves the understanding of the molecular mechanisms influenced by these drugs and could help refine the development of future targeted therapies for treating diabetes and obesity. Incretin receptor agonists are a class of drugs that mimic the effects of incretin hormones - glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) - to stimulate insulin secretion and regulate blood sugar levels."
"At pharmacologic dosing, they also signal to the brain the feeling of prolonged fullness and satiety, resulting in weight loss. These drugs, more commonly known as GLP-1 and GLP-1/GIP receptor agonist drugs (marketed as semaglutide and tirzepatide), have been commonly prescribed for the treatment of diabetes, and more recently, the management of obesity. Nonetheless, the neural mechanisms by which these drugs regulate appetite and what areas of the brain these drugs specifically interact with has remained poorly understood."
""We've known for several years now that the way these drugs induce weight loss is by actions on the brain and largely by curbing appetite, but the brain's obviously an incredibly complicated organ and a big question has been where in the brain these drugs might act," Beutler said. In the current study, Beutler's team aimed to better understand how GLP-1 and GIP receptor agonist drugs affect the activity of AgRP neurons, a subset of neurons localized in the brain's hypothalamus that are known to regulate appetite."
Semaglutide and tirzepatide modulate novel neural circuits that suppress appetite by influencing hypothalamic pathways. These drugs are GLP-1 and GLP-1/GIP receptor agonists that mimic incretin hormones (GLP-1 and GIP), stimulate insulin secretion, and help regulate blood glucose. At pharmacologic doses, they signal prolonged fullness and satiety to the brain, producing weight loss. The agents have been prescribed for diabetes and increasingly for obesity management. The specific neural mechanisms and brain regions mediating appetite suppression were previously poorly understood. In vivo fiber photometry was used to measure AgRP neuron activity in fasted mice to clarify drug effects on appetite-regulating neurons.
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