ReviewDelineating the regulation of energy homeostasis using hypothalamic cell models

•Hypothalamic neurons integrate signals to control energy homeostasis.•Animal and cell models are used to delineate hypothalamic neuropeptide regulation.•Both in vivo and in vitro models provide key advantages and challenges.•Immortalized models of hypothalamic neurons are tools to study neuronal cell biology.•Specific models decipher aspects of NPY/AgRP, proglucagon, and POMC neuronal function.

Attesting to its intimate peripheral connections, hypothalamic neurons integrate nutritional and hormonal cues to effectively manage energy homeostasis according to the overall status of the system. Extensive progress in the identification of essential transcriptional and post-translational mechanisms regulating the controlled expression and actions of hypothalamic neuropeptides has been identified through the use of animal and cell models. This review will introduce the basic techniques of hypothalamic investigation both in vivo and in vitro and will briefly highlight the key advantages and challenges of their use. Further emphasis will be place on the use of immortalized models of hypothalamic neurons for in vitro study of feeding regulation, with a particular focus on cell lines proving themselves most fruitful in deciphering fundamental basics of NPY/AgRP, Proglucagon, and POMC neuropeptide function.