Journal Article

Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice

Xu, Yong, Zhang, Zhi, Reis, Fernando M. C. V., Park, Jae W., Liesa, Marc, Shum, Michael, Paul, Ketema, Sivakumar, Nilla, Massa, Megan G., He, Yanlin, Ajijola, Olujimi A., van Veen, J. Edward, Adhikari, Avishek, Correa, Stephanie M., DiVittorio, Johnathon R., Anderson, Shawn, Maesta-Pereira, Sandra, Nichols, India

2020

Overview

Homeotherms maintain a stable internal body temperature despite changing environments. During energy deficiency, some species can cease to defend their body temperature and enter a hypothermic and hypometabolic state known as torpor. Recent advances have revealed the medial preoptic area (MPA) as a key site for the regulation of torpor in mice. The MPA is estrogen-sensitive and estrogens also have potent effects on both temperature and metabolism. Here, we demonstrate that estrogen-sensitive neurons in the MPA can coordinate hypothermia and hypometabolism in mice. Selectively activating estrogen-sensitive MPA neurons was sufficient to drive a coordinated depression of metabolic rate and body temperature similar to torpor, as measured by body temperature, physical activity, indirect calorimetry, heart rate, and brain activity. Inducing torpor with a prolonged fast revealed larger and more variable calcium transients from estrogen-sensitive MPA neurons during bouts of hypothermia. Finally, whereas selective ablation of estrogen-sensitive MPA neurons demonstrated that these neurons are required for the full expression of fasting-induced torpor in both female and male mice, their effects on thermoregulation and torpor bout initiation exhibit differences across sex. Together, these findings suggest a role for estrogen-sensitive MPA neurons in directing the thermoregulatory and metabolic responses to energy deficiency. Torpor is a state of reduced metabolism and body temperature that conserves energy when food is scarce. Here the authors show that estrogen-sensitive neurons in the hypothalamus regulate torpor in mice, maintaining torpor in both sexes but initiating torpor and regulating core temperature differentially across sex.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 42/44 / 49/91 / 631/378/3920 / 631/443/319 / 64/60 / 9/25 / 9/26 / Ablation / Animals / Body temperature / Body Temperature - genetics / Body Temperature - physiology / Body Temperature Regulation - physiology / Calcium / Calorimetry / Changing environments / Energy / Energy conservation / Energy Metabolism - physiology / Environmental changes / Estrogen Receptor alpha - genetics / Estrogen Receptor alpha - metabolism / Estrogens / Estrogens - metabolism / Fasting / Female / Heart rate / Homeotherms / Humanities and Social Sciences / Hypometabolism / Hypothalamus / Hypothermia / Hypothermia - genetics / Hypothermia - metabolism / Male / Metabolic rate / Metabolic response / Metabolism / Mice / Mice, Inbred C57BL / Mice, Knockout / multidisciplinary / Neurons / Neurons - physiology / Physical activity / Preoptic area / Preoptic Area - metabolism / Science / Science (multidisciplinary) / Sex / Thermoregulation / Torpor / Torpor - physiology