A Subpopulation of Hypothalamic Neurons Expressing an Olfactory Related Protein Controls Energy Homeostasis
1 Max Planck Institute for Metabolism Research
2 Max Planck Institute for Metabolism Research / Cologne Excellence Cluster on Aging and Aging-Associated Diseases
Olfaction is a crucial sense for integrating a variety of external information, from presence and evaluation of food sources to detection of predators. However, key factors of the olfactory system, such as olfactory receptors and olfactory-related signalling molecules, are ectopically expressed and functionally relevant throughout the mammalian organism. Our group has characterized hypothalamic neuronal populations expressing the olfactory marker protein (OMP). OMP has long been used as a marker to specifically target mature olfactory sensory neurons and has recently been identified as an essential modulator of the olfactory signal transduction cascade. Using a complementary set of approaches, including virus-based mapping and chemogenetics, we uncovered the molecular profile, projection patterns and role in energy homeostasis of an OMP-expressing hypothalamic neuronal subpopulation. We determined OMP to be predominantly expressed in the anterior paraventricular nucleus of the hypothalamus (PVH), which is strongly implicated in feeding and energy homeostasis. Single-cell transcriptomics analysis revealed PVHOMP neurons’ distinct molecular phenotype and co-expression with specific neuropeptides. PVHOMP neurons project to several hypothalamic nuclei fundamental to central nervous control of metabolism, such as the arcuate hypothalamic nucleus and the preoptic area. Targeted chemogenetic activation of PVHOMP neurons resulted in enhanced thermoregulation and subsequent alterations in metabolic parameters, while no major acute alterations in feeding behaviour were observed. In conclusion, we have uncovered a novel functional role for a PVH subpopulation that ectopically expresses an olfaction-related protein, revealing it as a novel potential player in central nervous control of energy homeostasis.