Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice

Zhi Zhang, Fernando M. C. V. Reis, Yanlin He, Jae W. Park, Johnathon R. DiVittorio, Nilla Sivakumar, J. Edward van Veen, Sandra Maesta-Pereira, Michael Shum, India Nichols, Megan G. Massa, Shawn Anderson, Ketema Paul, Marc Liesa, Olujimi A. Ajijola, Yong Xu, Avishek Adhikari and Stephanie M. Correa ()
Additional contact information
Zhi Zhang: University of California Los Angeles
Fernando M. C. V. Reis: University of California Los Angeles
Yanlin He: USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine
Jae W. Park: University of California Los Angeles
Johnathon R. DiVittorio: University of California Los Angeles
Nilla Sivakumar: University of California Los Angeles
J. Edward van Veen: University of California Los Angeles
Sandra Maesta-Pereira: University of California Los Angeles
Michael Shum: David Geffen School of Medicine
India Nichols: University of California Los Angeles
Megan G. Massa: University of California Los Angeles
Shawn Anderson: University of California Los Angeles
Ketema Paul: University of California Los Angeles
Marc Liesa: David Geffen School of Medicine
Olujimi A. Ajijola: UCLA Cardiac Arrhythmia Center, Department of Medicine, David Geffen School of Medicine
Yong Xu: USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine
Avishek Adhikari: University of California Los Angeles
Stephanie M. Correa: University of California Los Angeles

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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 estrogen-sensitive MPA neurons in directing the thermoregulatory and metabolic responses to energy deficiency.

Date: 2020
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DOI: 10.1038/s41467-020-20050-1

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