biostudies-literatureAmeroso DU.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and StrokeNIDDK NIH HHSNINDS NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases627-643https://www.ebi.ac.uk/biostudies/studies/S-EPMC9177635biostudies-literatureUnknown4(5)Brain-derived neurotrophic factor (BDNF) is essential for maintaining energy and glucose balance within the central nervous system. Because the study of its metabolic actions has been limited to effects in neuronal cells, its role in other cell types within the brain remains poorly understood. Here we show that astrocytic BDNF signaling within the ventromedial hypothalamus (VMH) modulates neuronal activity in response to changes in energy status. This occurs via the truncated TrkB.T1 receptor. Accordingly, either fasting or central BDNF depletion enhances astrocytic synaptic glutamate clearance, thereby decreasing neuronal activity in mice. Notably, selective depletion of TrkB.T1 in VMH astrocytes blunts the effects of energy status on excitatory transmission, as well as on responses to leptin, glucose and lipids. These effects are driven by increased astrocytic invasion of excitatory synapses, enhanced glutamate reuptake and decreased neuronal activity. We thus identify BDNF/TrkB.T1 signaling in VMH astrocytes as an essential mechanism that participates in energy and glucose homeostasis.Nature metabolismAstrocytic BDNF signaling within the ventromedial hypothalamus regulates energy homeostasis.PMC91776351R01DK117935T32DK124170T32 DK124170T32 NS0617645T32NS0617641R21NS091871R01 DK117935F31DK118789R21 NS091871R01 NS113499F31 DK118789Rios MMeng AAmeroso DDulla CGFelsted JChen SfalseAstrocytic BDNF signaling within the ventromedial hypothalamus regulates energy homeostasis.Brain-derived neurotrophic factor (BDNF) is essential for maintaining energy and glucose balance within the central nervous system. Because the study of its metabolic actions has been limited to effects in neuronal cells, its role in other cell types within the brain remains poorly understood. Here we show that astrocytic BDNF signaling within the ventromedial hypothalamus (VMH) modulates neuronal activity in response to changes in energy status. This occurs via the truncated TrkB.T1 receptor. Accordingly, either fasting or central BDNF depletion enhances astrocytic synaptic glutamate clearance, thereby decreasing neuronal activity in mice. Notably, selective depletion of TrkB.T1 in VMH astrocytes blunts the effects of energy status on excitatory transmission, as well as on responses to leptin, glucose and lipids. These effects are driven by increased astrocytic invasion of excitatory synapses, enhanced glutamate reuptake and decreased neuronal activity. We thus identify BDNF/TrkB.T1 signaling in VMH astrocytes as an essential mechanism that participates in energy and glucose homeostasis.2022-01-01T00:00:00Z2022 May2025-04-05T13:44:38.023Z2025-04-05T13:44:38.023ZS-EPMC91776353550159910.1038/s42255-022-00566-0