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Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress

Compelling evidence has shown that, besides its putative effect on the regulation of the gonadal axis, estradiol (E2) exerts a dichotomic effect on the hypothalamus to regulate food intake and energy expenditure. The anorectic effect of E2 is mainly mediated by its action on the arcuate nucleus (ARC...

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Autores principales: González-García, Ismael, Contreras, Cristina, Estévez-Salguero, Ánxela, Ruíz-Pino, Francisco, Colsh, Benoit, Pensado, Iván, Liñares-Pose, Laura, Rial-Pensado, Eva, Martínez de Morentin, Pablo B., Fernø, Johan, Diéguez, Carlos, Nogueiras, Rubén, Le Stunff, Hervé, Magnan, Christophe, Tena-Sempere, Manuel, López, Miguel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198289/
https://www.ncbi.nlm.nih.gov/pubmed/30304681
http://dx.doi.org/10.1016/j.celrep.2018.09.038
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author González-García, Ismael
Contreras, Cristina
Estévez-Salguero, Ánxela
Ruíz-Pino, Francisco
Colsh, Benoit
Pensado, Iván
Liñares-Pose, Laura
Rial-Pensado, Eva
Martínez de Morentin, Pablo B.
Fernø, Johan
Diéguez, Carlos
Nogueiras, Rubén
Le Stunff, Hervé
Magnan, Christophe
Tena-Sempere, Manuel
López, Miguel
author_facet González-García, Ismael
Contreras, Cristina
Estévez-Salguero, Ánxela
Ruíz-Pino, Francisco
Colsh, Benoit
Pensado, Iván
Liñares-Pose, Laura
Rial-Pensado, Eva
Martínez de Morentin, Pablo B.
Fernø, Johan
Diéguez, Carlos
Nogueiras, Rubén
Le Stunff, Hervé
Magnan, Christophe
Tena-Sempere, Manuel
López, Miguel
author_sort González-García, Ismael
collection PubMed
description Compelling evidence has shown that, besides its putative effect on the regulation of the gonadal axis, estradiol (E2) exerts a dichotomic effect on the hypothalamus to regulate food intake and energy expenditure. The anorectic effect of E2 is mainly mediated by its action on the arcuate nucleus (ARC), whereas its effects on brown adipose tissue (BAT) thermogenesis occur in the ventromedial nucleus (VMH). Here, we demonstrate that central E2 decreases hypothalamic ceramide levels and endoplasmic reticulum (ER) stress. Pharmacological or genetic blockade of ceramide synthesis and amelioration of ER stress selectively occurring in the VMH recapitulate the effect of E2, leading to increased BAT thermogenesis, weight loss, and metabolic improvement. These findings demonstrate that E2 regulation of ceramide-induced hypothalamic lipotoxicity and ER stress is an important determinant of energy balance, suggesting that dysregulation of this mechanism may underlie some changes in energy homeostasis seen in females.
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spelling pubmed-61982892018-10-25 Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress González-García, Ismael Contreras, Cristina Estévez-Salguero, Ánxela Ruíz-Pino, Francisco Colsh, Benoit Pensado, Iván Liñares-Pose, Laura Rial-Pensado, Eva Martínez de Morentin, Pablo B. Fernø, Johan Diéguez, Carlos Nogueiras, Rubén Le Stunff, Hervé Magnan, Christophe Tena-Sempere, Manuel López, Miguel Cell Rep Article Compelling evidence has shown that, besides its putative effect on the regulation of the gonadal axis, estradiol (E2) exerts a dichotomic effect on the hypothalamus to regulate food intake and energy expenditure. The anorectic effect of E2 is mainly mediated by its action on the arcuate nucleus (ARC), whereas its effects on brown adipose tissue (BAT) thermogenesis occur in the ventromedial nucleus (VMH). Here, we demonstrate that central E2 decreases hypothalamic ceramide levels and endoplasmic reticulum (ER) stress. Pharmacological or genetic blockade of ceramide synthesis and amelioration of ER stress selectively occurring in the VMH recapitulate the effect of E2, leading to increased BAT thermogenesis, weight loss, and metabolic improvement. These findings demonstrate that E2 regulation of ceramide-induced hypothalamic lipotoxicity and ER stress is an important determinant of energy balance, suggesting that dysregulation of this mechanism may underlie some changes in energy homeostasis seen in females. Cell Press 2018-10-09 /pmc/articles/PMC6198289/ /pubmed/30304681 http://dx.doi.org/10.1016/j.celrep.2018.09.038 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
González-García, Ismael
Contreras, Cristina
Estévez-Salguero, Ánxela
Ruíz-Pino, Francisco
Colsh, Benoit
Pensado, Iván
Liñares-Pose, Laura
Rial-Pensado, Eva
Martínez de Morentin, Pablo B.
Fernø, Johan
Diéguez, Carlos
Nogueiras, Rubén
Le Stunff, Hervé
Magnan, Christophe
Tena-Sempere, Manuel
López, Miguel
Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress
title Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress
title_full Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress
title_fullStr Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress
title_full_unstemmed Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress
title_short Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress
title_sort estradiol regulates energy balance by ameliorating hypothalamic ceramide-induced er stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198289/
https://www.ncbi.nlm.nih.gov/pubmed/30304681
http://dx.doi.org/10.1016/j.celrep.2018.09.038
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