Warm Responsive Neurons in the Hypothalamic Preoptic Area Are Potent Regulators of Glucose Homeostasis in Male Mice

When mammals are exposed to a warm environment, overheating is prevented by activation of "warm-responsive" neurons (WRNs) in the hypothalamic preoptic area (POA) that reduce thermogenesis while promoting heat dissipation. Heat exposure also impairs glucose tolerance, but whether this also results from activation of POA WRNs is unknown. To address this question, we sought in the current work to determine if glucose intolerance induced by heat exposure can be attributed to activation of a specific subset of WRNs that express pituitary adenylate cyclase-activating peptide (ie, POAPacap neurons). We report that when mice are exposed to an ambient temperature sufficiently warm to activate POAPacap neurons, the expected reduction of energy expenditure is associated with glucose intolerance, and that these responses are recapitulated by chemogenetic POAPacap neuron activation. Because heat-induced glucose intolerance was not blocked by chemogenetic inhibition of POAPacap neurons, we conclude that POAPacap neuron activation is sufficient, but not required, to explain the impairment of glucose tolerance elicited by heat exposure.