Format

Send to

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

Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK.

Author information

1
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.
2
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.
3
Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands; Department of Hypothalamic Integration Mechanisms, Netherlands Institute of Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Science, Amsterdam, 1105 BA, The Netherlands; Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Chinese Academy of Sciences, Hefei, Anhui, 230026, P. R. China.
4
Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
5
Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, 15782, Spain.
6
Diabetes Research Unit, EBRC-827, Boston Medical Center, Boston, MA 02118, USA.
7
Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands; Department of Hypothalamic Integration Mechanisms, Netherlands Institute of Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Science, Amsterdam, 1105 BA, The Netherlands.
8
Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.
9
Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA; Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
10
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. Electronic address: m.lopez@usc.es.

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.

PMID:
24856932
PMCID:
PMC4082097
DOI:
10.1016/j.cmet.2014.03.031
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center