Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK.
Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK.
复制标题
DOI：
10.1016/j.cmet.2014.03.031
复制
发表时间：
2014-07-01
期刊：
影响因子：
29
通讯作者：
López M
中科院分区：
文献类型：
--
作者：
Martínez de Morentin PB;González-García I;Martins L;Lage R;Fernández-Mallo D;Martínez-Sánchez N;Ruíz-Pino F;Liu J;Morgan DA;Pinilla L;Gallego R;Saha AK;Kalsbeek A;Fliers E;Bisschop PH;Diéguez C;Nogueiras R;Rahmouni K;Tena-Sempere M;López M
雌激素通过中枢和外周作用在调节能量平衡中发挥重要作用。在这里，我们证明了雌二醇（E2）的中枢作用通过雌激素受体α（ERα）选择性地抑制下丘脑腹内侧核（VMH）的AMP激活的蛋白激酶（AMPK），导致通过交感神经系统（SNS）以非摄食依赖的方式激活棕色脂肪组织（BAT）的产热。VMH中AMPK的遗传激活阻止了E2诱导的BAT介导的产热和体重减轻的增加。值得注意的是，在动情周期E2水平的波动也调节这个综合的生理网络。总之，这些研究结果表明，E2调节VMH AMPK-SNS-BAT轴是能量平衡的重要决定因素，并表明该轴的失调可能导致与女性性腺轴功能障碍相关的能量稳态和肥胖的常见变化。中枢雌二醇（E2）促进负能量平衡中枢E2增加产热性交感神经活动中枢E2通过ERα抑制AMPK，特别是在VMH中VMH AMPK-SNS-BAT轴介导E2对能量平衡的中枢作用雌激素在体重调节中起重要作用。Martínez de Morentin及其同事表明，雌二醇（E2）通过雌激素受体α发挥作用，选择性地抑制大脑下丘脑腹内侧核中的能量传感器AMPK，从而激活棕色脂肪组织中的产热作用。
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. Central estradiol (E2) promotes negative energy balance Central E2 increases thermogenic sympathetic nerve activity Central E2 inhibits AMPK, specifically in the VMH, through ERα The VMH AMPK-SNS-BAT axis mediates the central actions of E2 on energy balance Estrogens play a major role in the regulation of body weight. Martínez de Morentin and colleagues show that estradiol (E2), acting through estrogen receptor alpha, selectively inhibits the energy sensor AMPK in the brain hypothalamic ventromedial nucleus, leading to activation of thermogenesis in brown adipose tissue.
登录
查看更多内容
影响因子：
5.2
作者：
Hill JW;Alreja M;Elias CF
通讯作者：
Elias CF
影响因子：
64.8
作者：
Minokoshi, Y;Kim, YB;Kahn, BB
通讯作者：
Kahn, BB
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.8
作者：
García, MC;López, M;Señarís, RM
通讯作者：
Señarís, RM
影响因子：
14.8
作者：
Carling, David;Mayer, Faith V.;Gamblin, Steven J.
通讯作者：
Gamblin, Steven J.