101-OR: Identification of Warm Sensitive Neurons in the Hypothalamic Preoptic Area as Powerful Regulators of Glucose Homeostasis

Inhibition of warm sensitive neurons (WSNs) in the hypothalamic preoptic area (POA) has been suggested to play a key role in the thermogenic response to cold exposure. As this response is enabled by a marked increase of insulin sensitivity in thermogenic tissues, we hypothesized that 1) WSN inhibition mediates metabolic as well as thermogenic responses to cold, and therefore, 2) WSN activation has the opposite effects. To test this hypothesis, we utilized DREADD technology to activate or inhibit a recently identified subpopulation of POA WSNs defined by their expression of the neuropeptide, Pacap, using the drug clozapine-N-oxide (CNO). We report that, pharmacogenetic activation of this POA WSN population found significant reductions in energy expenditure (Sal vs. CNO: 0.32±0.10 vs. 0.21±0.02 kcal/hr; p