Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • AMP-Activated Protein Kinases / chemistry
  • AMP-Activated Protein Kinases / metabolism*
  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Energy Metabolism / drug effects
  • Estradiol / pharmacology*
  • Estrogen Receptor alpha / metabolism
  • Female
  • Hypothalamus / drug effects*
  • Hypothalamus / enzymology
  • Hypothalamus / metabolism
  • Ovary / injuries
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Sympathetic Nervous System / metabolism
  • Thermogenesis / drug effects*


  • Estrogen Receptor alpha
  • Estradiol
  • AMP-Activated Protein Kinases