The hypothalamus is the central regulator of homeostasis with proopiomelanocortin (POMC) neurons in the arcuate nucleus playing a fundamental role. These neurons release neuropeptides that promote energy expenditure and satiety and are a target for leptin, an anorexigenic hormone of adipose tissue origin. POMC neurons communicate with hypothalamic astrocytes via extracellular vesicles (EVs) that contain proteins, lipids, and nucleic acids, and relay information regarding metabolic status. Our hypothesis is that astrocytes affect neuronal function and leptin signaling pathway in a nutrition-dependent manner. Primary hypothalamic astrocyte cultures were treated with 0.5 mM palmitic (PA), oleic (OA) or vehicle for 24 hours (h). EVs purified from the media (EV-PA, EV-OA or EV-V, respectively) were applied to the mHypoA-POMC/GFP-2 neuronal cell line for 4 or 24 h. POMC expression increased at 4 and 24 h in response to leptin and EV-OA, but treatment with EV-PA stimulated it only at 4 h. However, co-treatment with leptin and EVs at 4 h did not increase POMC expression, whereas at 24 h it induced POMC expression much more than the isolated treatments. This may be due to the effect of EVs on leptin signaling pathways. Preliminary results indicate that a repressor of POMC transcription, the thyroid transcription factor (TTF-1), is decreased after 24 h of treatment with EVs, whereas leptin has no effect on this protein. Therefore, EVs from hypothalamic astrocytes could contain biological molecules, such as miRNAs, that modulate the leptin signaling pathway (e.g., FOXO1, Akt, etc.) affecting POMC transcription in these neurons.