Topic: semaglutide

Glucagon like peptide (GLP-1) receptor agonists (GLP-1 RAs), such as Semaglutide, suppress food intake and are FDA approved to treat obesity. The primary mechanism of GLP-1 RAs involves interactions with the central nervous system, where GLP1 RA act in the hypothalamus or brainstem to reduce food intake. GLP-1 action on midbrain dopamine neurons in the VTA may also reduce food motivation and reward to suppress appetite. In addition to GLP1 RAs, new compounds with dual GLP1R and glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonism, such as tirzepatide, show greater weight loss

The long-acting GLP-1 analogue semaglutide has revolutionized the pharmacological treatment of obesity, but the brain-mediated mechanisms behind the body weight loss and its most common side effect, nausea, remain unclear. By using select delivery of a Cre-dependent viral vector encoding hM3DGq and mCherry into the dorsal vagal complex (DVC) of TRAP2 mice, we here show that neurons in the DVC that are activated by semaglutide have direct projections to a variety of brainstem and forebrain structures involved in appetite regulation and visceral malaise. CNO-mediated re-activation of DVC neurons