Topic: nausea

GFRAL-expressing neurons actuate aversion and nausea, are targets for obesity treatment and may mediate metformin effects by long-term GDF15-GFRAL agonism. If GFRAL+ neurons acutely regulate glucose and energy homeostasis is however underexplored. Here, we report that cell-specific activation of GFRAL+ neurons using a variety of techniques causes a torpor-like state, including hypothermia, the release of stress hormones, a shift from glucose to lipid oxidation, and impaired insulin sensitivity, glucose tolerance and skeletal muscle glucose uptake but augmented glucose uptake in visceral fat. M

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