PARAVENTRICULAR NEURONS EXPRESSING OLFACTORY MARKER PROTEIN CONTROL METABOLISM AND GLUCOSE HOMEOSTASIS

Olfaction is a crucial sense to gain a variety of external information from presence and evaluation of food sources to the early detection of predators. However, factors considered primarily associated with olfactory function, such as olfactory receptors, are ectopically expressed and functionally relevant throughout the mammalian organism. Here, we identified a distinct subpopulation of the anterior PVH which expresses the Olfactory Marker Protein (OMP), an important player in olfactory signal transduction and circuit formation commonly used as a marker for mature olfactory sensory neurons of the olfactory epithelium. Our analysis of published single-cell RNA-sequencing datasets and histological methods revealed these to be a subset of non-neuroendocrine TRH/PACAP neurons which project to other hypothalamic nuclei controlling whole-body metabolism. Chemogenetic activation of PVH^OMP neurons altered carbohydrate utilisation and glucose homeostasis, revealing them to play a role in metabolic functions. Furthermore, an increase in thermoregulation and activity was observed. Since OMP is an important regulator of intracellular mechanisms and downstream efferents in olfaction, the question arises as to how this protein is involved in the hypothalamic control of metabolism. We observed an effect of fasting on OMP transcription, suggesting a role in the regulation of feeding behaviour and energy homeostasis. Ongoing studies aim to investigate the functionality of this potential novel player in hypothalamic neuronal modulation. Overall, we identified an OMP-expressing subpopulation of paraventricular neurons whose function in metabolic regulation could depend on the protein’s capability to influence intracellular messaging.