AGRP neurons are a hypothalamic population that senses physiological energy deficit and consequently increases appetite. Molecular and cellular processes for energy-sensing and elevated neuronal output are critical for understanding the central nervous system response to energy deficit states, such as during weight-loss. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss but, in adult mice, this has been limited by technical challenges. We report high-quality gene expression profiles of AGRP neurons under well-fed and energy deficit states. For comparison, we also analyzed POMC neurons, an intermingled population that suppresses appetite. This data newly identifies cell type-selective involvement of signaling pathways, ion channels, neuropeptides, and G-protein coupled receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders. Overall design: Examination of 2 different neuronal cell types under 2 conditions.