Synaptic re-organization of hypothalamic feeding circuits in response to metabolic shifts involves neurons as well as astrocytes, cells that can directly respond to the metabolic hormone, leptin, in vitro. The role of glia cells in hypothalamic synaptic adaptions had been unclear. We have recently shown that leptin receptors are expressed in hypothalamic astrocytes and that conditional, adult deletion of leptin receptors in astrocytes leads to altered glial morphology, decreased glial coverage and elevated synaptic inputs onto hypothalamic arcuate neurons such as pro-opiomelanocortin (POMC)- and Agouti-related protein (AgRP)-producing neurons. Leptin-induced suppression of feeding was reduced, while rebound feeding after fasting or ghrelin administration was elevated in mice with astrocyte-specific leptin receptor deficiency. These data unmask an active role of glial cells in the initiation of hypothalamic synaptic plasticity and neuroendocrine control of feeding by leptin.