Diverse roles of hypothalamic proopiomelanocortin (POMC) neuronal subpopulations in energy homeostasis: investigating the cholinergic’s functions and projection.

Obesity and diabetes are major public health challenges driven by disruptions in metabolic homeostasis. The hypothalamic arcuate nucleus (Arc) is a critical integrative center for the regulation of energy and glucose homeostasis. Arcuate proopiomelanocortin (POMC) neurons are canonically recognized for suppressing food intake and promoting energy expenditure when activated. However, their role in glucose regulation remains controversial, with divergent effects reported depending on hormonal signalling pathways engaged and autonomic efferences recruited. This heterogeneity may partly stem from the fact that Arc-POMC neurons are not a uniform population but comprise distinct subpopulations according to their neurotransmitter profiles and projection targets. In particular, the roles of other Arc-POMC subpopulations are still poorly understood; one of these co-releases acetylcholine (ChAT-POMC), yet whether they contribute to the regulation of energy and glucose homeostasis remains unknown. In this study, we investigated the functional role of ChAT-POMC neurons: our preliminary findings suggest that these may play a selective role in glucose regulation. Characterizing the physiological functions of distinct Arc-POMC subpopulations may reveal novel neural pathways linking central circuits to peripheral metabolism and ultimately help develop new targeted therapeutic treatments for obesity and diabetes.