BODY TEMPERATURE GOVERNS GLUCOSE METABOLISM DURING SYNTHETIC HIBERNATION

To survive in harsh environment such as food shortages in cold seasons, some animals develop a specific physiologic state—the hibernation. Recently, a hibernation-like state was successfully induced in non-hibernators such as mice. This state is induced by activation of Qrfp neurons in the preoptic area of the hypothalamus and is called Q-neuron-induced hypothermia and hypometabolism (QIH) (Takahashi et al., Nature, 2020). The mice showed hypothermia with very low systemic oxygen consumption during QIH. However, it remains unclear how the metabolism of glucose, the main energy resource, is regulated during QIH. In this study, we induced QIH by using DREADD to chemogenetically activate the Qrfp neurons of mice and found that the QIH mice were insulin resistant with systemic glucose hypometabolism. These mice showed hyperinsulinemia and higher blood glucose after overnight fasting, suggesting that the QIH animals are in a diabetes-like metabolic state. Surprisingly, the glucose metabolism was fully recovered in an elevated ambient temperature (34℃), in which the body temperature of QIH mice was comparable with normal mice. QIH-induced suppression of appetite and locomotor activities were also partially recovered under the elevated ambient temperature. We concluded that activation of Qrfp neurons induced insulin resistance and glucose hypometabolism, which can be recovered by increasing body temperature. These results indicate that the Qrfp neurons do not directly control glucose metabolism during QIH. Instead, hypothermia alters glucose metabolism, appetite, and locomotor activity.