Do POMC neurons have a sweet tooth for leptin? Special issue: Role of nutrients in nervous control of energy balance

Coordinated detection of changes in metabolic state by the nervous system is fundamental for survival. Hypothalamic pro-opiomelanocortin (POMC) neurons play a critical role in integrating metabolic signals, including leptin levels. They also coordinate adaptative responses and thus represent an important relay in the regulation of energy balance. Despite a plethora of work documenting the effects of individual hormones, nutrients, and neuropeptides on POMC neurons, the importance for crosstalk and additive effects between such signaling molecules is still underexplored. The ability of the metabolic state and the concentrations of nutrients, such as glucose, to influence leptin's effects on POMC neurons appears critical for understanding the function and complexity of this regulatory network. Here, we summarize the current knowledge on the effects of leptin on POMC neuron electrical excitability and discuss factors potentially contributing to variability in these effects, with a particular focus on the mouse models that have been developed and the importance of extracellular glucose levels. This review highlights the importance of the metabolic "environment" for determining hypothalamic neuronal responsiveness to metabolic cues and for determining the fundamental effects of leptin on the activity of hypothalamic POMC neurons.