Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK

Pablo Blanco Martinez De Morentin; Ismael Gonzalez-Garcia; Luis Martins; Ricardo Lage; Diana  Fernandez-Mallo; Noelia Martinez-Sanchez; Francisco Ruiz-Pino; Ji Liu; Donald A Morgan; Leonor  Pinilla; Rosalia Gallego; Asish K Saha; Andries Kalsbeek; Eric Fliers; Peter H.  Bisschop; Carlos Dieguez; Ruben Nogueiras; Kamal Rahmouni; Manuel  Tena-Sempere; Miguel Lopez

doi:10.1016/j.cmet.2014.03.031

Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK

Pablo Blanco Martinez De Morentin, Ismael Gonzalez-Garcia, Luis Martins, Ricardo Lage, Diana Fernandez-Mallo, Noelia Martinez-Sanchez, Francisco Ruiz-Pino, Ji Liu, Donald A Morgan, Leonor Pinilla, Rosalia Gallego, Asish K Saha, Andries Kalsbeek, Eric Fliers, Peter H. Bisschop, Carlos Dieguez, Ruben Nogueiras, Kamal Rahmouni, Manuel Tena-Sempere, Miguel Lopez

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

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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

Original language	English
Pages (from-to)	41-53
Number of pages	13
Journal	Cell Metabolism
Volume	20
Issue number	1
Early online date	22 May 2014
DOIs	https://doi.org/10.1016/j.cmet.2014.03.031
Publication status	Published - Jul 2014

Keywords

AMP-Activated Protein Kinases
Adipose Tissue, Brown
Animals
Energy Metabolism
Estradiol
Estrogen Receptor alpha
Female
Hypothalamus
Ovary
Rats
Rats, Sprague-Dawley
Rats, Wistar
Sympathetic Nervous System
Thermogenesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cmet.2014.03.031Licence: CC BY-NC-ND

Estradiol Regulates Brown Adipose Tissue
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial-No Derivs (CC BY-NC-ND 3.0) license, which permits others to distribute this work non-commercially provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc-nd/3.0/
Final published version, 3.47 MBLicence: CC BY-NC-ND

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Martinez De Morentin, P. B., Gonzalez-Garcia, I., Martins, L., Lage, R., Fernandez-Mallo, D., Martinez-Sanchez, N., Ruiz-Pino, F., Liu, J., Morgan, D. A., Pinilla, L., Gallego, R., Saha, A. K., Kalsbeek, A., Fliers, E., Bisschop, P. H., Dieguez, C., Nogueiras, R., Rahmouni, K., Tena-Sempere, M., & Lopez, M. (2014). Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK. Cell Metabolism, 20(1), 41-53. https://doi.org/10.1016/j.cmet.2014.03.031

Martinez De Morentin, PB, Gonzalez-Garcia, I, Martins, L, Lage, R, Fernandez-Mallo, D, Martinez-Sanchez, N, Ruiz-Pino, F, Liu, J, Morgan, DA, Pinilla, L, Gallego, R, Saha, AK, Kalsbeek, A, Fliers, E, Bisschop, PH, Dieguez, C, Nogueiras, R, Rahmouni, K, Tena-Sempere, M & Lopez, M 2014, 'Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK', Cell Metabolism, vol. 20, no. 1, pp. 41-53. https://doi.org/10.1016/j.cmet.2014.03.031

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title = "Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK",

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",

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AU - Martinez De Morentin, Pablo Blanco

AU - Gonzalez-Garcia, Ismael

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AU - Lage, Ricardo

AU - Fernandez-Mallo, Diana

AU - Martinez-Sanchez, Noelia

AU - Ruiz-Pino, Francisco

AU - Liu, Ji

AU - Morgan, Donald A

AU - Pinilla, Leonor

AU - Gallego, Rosalia

AU - Saha, Asish K

AU - Kalsbeek, Andries

AU - Fliers, Eric

AU - Bisschop, Peter H.

AU - Dieguez, Carlos

AU - Nogueiras, Ruben

AU - Rahmouni, Kamal

AU - Tena-Sempere, Manuel

AU - Lopez, Miguel

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KW - Hypothalamus

KW - Ovary

KW - Rats

KW - Rats, Sprague-Dawley

KW - Rats, Wistar

KW - Sympathetic Nervous System

KW - Thermogenesis

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SP - 41

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JO - Cell Metabolism

JF - Cell Metabolism

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Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK

Abstract

Keywords

UN SDGs

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