TY - JOUR
T1 - Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK
AU - Martínez de Morentin, Pablo B
AU - González-García, Ismael
AU - Martins, Luís
AU - Lage, Ricardo
AU - Fernández-Mallo, Diana
AU - Martínez-Sánchez, Noelia
AU - Ruíz-Pino, Francisco
AU - Liu, Ji
AU - Morgan, Donald A
AU - Pinilla, Leonor
AU - Gallego, Rosalía
AU - Saha, Asish K
AU - Kalsbeek, A.
AU - Fliers, Eric
AU - Bisschop, Peter H
AU - Diéguez, Carlos
AU - Nogueiras, Rubén
AU - Rahmouni, Kamal
AU - Tena-Sempere, Manuel
AU - López, Miguel
N1 - Copyright © 2014 Elsevier Inc. All rights reserved.
PY - 2014/7/1
Y1 - 2014/7/1
N2 - Estrogens play a major role in the modulation of energy balance through central and peripheral actions. Here, we demonstrate that central action of estradiol (E2) inhibits AMP-activated protein kinase (AMPK) through estrogen receptor alpha (ERα) selectively in the ventromedial nucleus of the hypothalamus (VMH), leading to activation of thermogenesis in brown adipose tissue (BAT) through the sympathetic nervous system (SNS) in a feeding-independent manner. Genetic activation of AMPK in the VMH prevented E2-induced increase in BAT-mediated thermogenesis and weight loss. Notably, fluctuations in E2 levels during estrous cycle also modulate this integrated physiological network. Together, these findings demonstrate that E2 regulation of the VMH AMPK-SNS-BAT axis is an important determinant of energy balance and suggest that dysregulation in this axis may account for the common changes in energy homeostasis and obesity linked to dysfunction of the female gonadal axis.
AB - Estrogens play a major role in the modulation of energy balance through central and peripheral actions. Here, we demonstrate that central action of estradiol (E2) inhibits AMP-activated protein kinase (AMPK) through estrogen receptor alpha (ERα) selectively in the ventromedial nucleus of the hypothalamus (VMH), leading to activation of thermogenesis in brown adipose tissue (BAT) through the sympathetic nervous system (SNS) in a feeding-independent manner. Genetic activation of AMPK in the VMH prevented E2-induced increase in BAT-mediated thermogenesis and weight loss. Notably, fluctuations in E2 levels during estrous cycle also modulate this integrated physiological network. Together, these findings demonstrate that E2 regulation of the VMH AMPK-SNS-BAT axis is an important determinant of energy balance and suggest that dysregulation in this axis may account for the common changes in energy homeostasis and obesity linked to dysfunction of the female gonadal axis.
U2 - 10.1016/j.cmet.2014.03.031
DO - 10.1016/j.cmet.2014.03.031
M3 - Article
C2 - 24856932
VL - 20
SP - 41
EP - 53
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 1
ER -