Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice

Authors: ZHANG, ZHI - UNIVERSITY OF CALIFORNIA (UCLA); REIS, FERNANDO - UNIVERSITY OF CALIFORNIA (UCLA); HE, YANLIN - PENNINGTON BIOMEDICAL RESEARCH CENTER; PARK, JAE - UNIVERSITY OF CALIFORNIA (UCLA); DIVITTORIO, JOHNATHON - UNIVERSITY OF CALIFORNIA (UCLA); SIVAKUMAR, NILLA - UNIVERSITY OF CALIFORNIA (UCLA); VAN VEEN, EDWARD - UNIVERSITY OF CALIFORNIA (UCLA); MAESTA-PEREIRA, SANDRA - UNIVERSITY OF CALIFORNIA (UCLA); SHUM, MICHAEL - GEFFEN SCHOOL OF MEDICINE; NICHOLS, INDIA - UNIVERSITY OF CALIFORNIA (UCLA); MASSA, MEGAN - UNIVERSITY OF CALIFORNIA (UCLA); ANDERSON, SHAWN - UNIVERSITY OF CALIFORNIA (UCLA); PAUL, KETEMA - GEFFEN SCHOOL OF MEDICINE; LIESA, MARC - GEFFEN SCHOOL OF MEDICINE; AJIJOLA, OLUJIMI - GEFFEN SCHOOL OF MEDICINE; XU, YONG - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); ADHIKARI, AVISHEK - UNIVERSITY OF CALIFORNIA (UCLA); CORREA, STEPHANIE - UNIVERSITY OF CALIFORNIA (UCLA)

Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/12/2020
Publication Date: 12/11/2020
Citation: Zhang, Z., Reis, F., He, Y., Park, J., Divittorio, J., Sivakumar, N., Van Veen, E., Maesta-Pereira, S., Shum, M., Nichols, I., Massa, M., Anderson, S., Paul, K., Liesa, M., Ajijola, O., Xu, Y., Adhikari, A., Correa, S. 2020. Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice. Nature Communications. 11:6378. https://doi.org/10.1038/s41467-020-20050-1.
DOI: https://doi.org/10.1038/s41467-020-20050-1

Interpretive Summary: Maintaining normal body temperature is essential for survival, but how it is regulated is not fully understood. Here we showed that a small group of cells in the brain can regulate body temperature and trigger torpor-like responses in animals. These findings identify novel brain mechanisms for the regulation of body temperature homeostasis.

Technical Abstract: 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 estrogensensitive MPA neurons in directing the thermoregulatory and metabolic responses to energy deficiency.