Obesity and diabetes are major public health challenges that arise from metabolic imbalance. The hypothalamic arcuate nucleus (Arc) is a key integrative hub in the regulation of energy and glucose homeostasis. Arcuate proopiomelanocortin (POMC) neurons reduce food intake and promote energy expenditure. However, they comprise distinct subpopulations defined by their neurotransmitter profile and projection targets. We previously found that GABAergic Arc-POMC projection to the dorsomedial hypothalamic nucleus (DMH) contributes to the regulation of feeding and body weight. Yet, the functional relevance of other Arc-POMC subpopulations remains poorly understood. A small subset of POMC neurons co-releases acetylcholine, but whether these cholinergic neurons participate in the control of energy and glucose balance is still unknown. In the present study, we investigated the role of POMC expression in cholinergic neurons and in neurons projecting to the DMH and the paraventricular nucleus (PVN). Our preliminary results suggest that whereas cholinergic POMC neurons may play a specific role in glucose regulation, POMC neurons projecting to the DMH and PVN, regardless of the neurotransmitter they co-release, may have a role in energy balance. Defining the physiological functions of distinct Arc-POMC subpopulations could uncover novel pathways linking central circuits to peripheral metabolism and pave the way for targeted therapeutic strategies against obesity and diabetes.