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雌二醇通过下丘脑AMPK调节棕色脂肪组织产热。

Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK.

作者信息

Martínez de Morentin Pablo B, González-García Ismael, Martins Luís, Lage Ricardo, Fernández-Mallo Diana, Martínez-Sánchez Noelia, Ruíz-Pino Francisco, Liu Ji, Morgan Donald A, Pinilla Leonor, Gallego Rosalía, Saha Asish K, Kalsbeek Andries, Fliers Eric, Bisschop Peter H, Diéguez Carlos, Nogueiras Rubén, Rahmouni Kamal, Tena-Sempere Manuel, López Miguel

机构信息

Department of Physiology, Research Center of Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, 15706, Spain.

CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, 15706, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, 14004 Spain; Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofia (HURS), Córdoba, 14004, Spain.

出版信息

Cell Metab. 2014 Jul 1;20(1):41-53. doi: 10.1016/j.cmet.2014.03.031. Epub 2014 May 22.

DOI:10.1016/j.cmet.2014.03.031
PMID:24856932
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4082097/
Abstract

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.

摘要

雌激素通过中枢和外周作用在能量平衡的调节中发挥主要作用。在此，我们证明雌二醇（E2）的中枢作用在下丘脑腹内侧核（VMH）中通过雌激素受体α（ERα）选择性地抑制AMP激活的蛋白激酶（AMPK），从而以不依赖进食的方式通过交感神经系统（SNS）激活棕色脂肪组织（BAT）中的产热作用。VMH中AMPK的基因激活可防止E2诱导的BAT介导的产热增加和体重减轻。值得注意的是，发情周期中E2水平的波动也会调节这个整合的生理网络。总之，这些发现表明E2对VMH AMPK-SNS-BAT轴的调节是能量平衡的一个重要决定因素，并表明该轴的失调可能解释了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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/89ea8adf507c/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/02fa95696237/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/9b7bc65ed9d3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/8ab5470e616a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/aea1e8cb0f7b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/fec9cf53d0c8/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/4d8619eead9f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/c29253bfc138/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/89ea8adf507c/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/02fa95696237/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/9b7bc65ed9d3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/8ab5470e616a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/aea1e8cb0f7b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/fec9cf53d0c8/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/4d8619eead9f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/c29253bfc138/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec48/4082097/89ea8adf507c/gr7.jpg

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