The physiological system implicated in the maintenance of energy homeostasis is situated predominantly in the hypothalamus. However, due to the inherent difficulty of studying individual neurons in the brain through in vivo analysis, cell models have been generated to investigate the direct action of hormones or other physiological compounds on metabolic effectors, such as neuropeptides, located in specific cell types from the hypothalamus. Immortalized, clonal cell lines represent an unlimited, homogeneous neuronal population that can be manipulated using a number of molecular techniques. In particular, cell lines have proven to be indispensable in the study of gene structure, gene expression and characterizing the molecular mechanisms responsible for regulating gene expression. In this review, we summarize recent studies that examine the direct transcriptional regulation of neuropeptide Y (NPY) by insulin and the leptin-mediated control of neurotensin (NT) gene expression. The use of these novel cell models has contributed profoundly to our understanding of how peripheral hormones, neuromodulators and neurontransmitters regulate transcriptional events that may ultimately contribute to the control of feeding behaviour.