mTOR signaling in the arcuate nucleus of the hypothalamus mediates the anorectic action of estradiol

Ismael González-García, Pablo B Martinez de Morentin, Ánxela Estévez-Salguero, Cristina Contreras, Amparo Romero-Picó , Johan Fernø, Ruben Nogueiras, Carlos Diéguez, Manuel Tena-Sempere, Sulay Tovar, Miguel López

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Abstract

Current evidence suggests that estradiol (E2), the main ovarian steroid, modulates energy balance by regulating both feeding and energy expenditure at the central level, through the energy sensor AMP-activated protein kinase (AMPK). We hypothesized that the hypothalamic mechanistic target of rapamycin (mTOR) pathway, a well-established nutrient sensor and modulator of appetite and puberty, could also mediate the anorectic effect of E2. Our data showed that, ovariectomy (OVX) elicited a marked downregulation of the mTOR signaling in the arcuate nucleus of the hypothalamus (ARC), an effect that was reversed by either E2 replacement or central estrogen receptor alpha (ERα) agonism. The significance of this molecular signaling was given by the genetic inactivation of S6 kinase B1 (S6K1, a key downstream mTOR effector) in the ARC, which prevented the E2-induced hypophagia and weight loss. Overall, these data indicate that E2 induces hypophagia through modulation of mTOR pathway in the ARC
Original languageEnglish
Pages (from-to)177-186
Number of pages9
JournalJournal of Endocrinology
Volume238
Issue number3
Early online date18 Jun 2018
DOIs
Publication statusPublished - Sep 2018

Fingerprint

Appetite Depressants
Arcuate Nucleus of Hypothalamus
Sirolimus
AIDS-Related Complex
Estradiol
Ribosomal Protein S6 Kinases
AMP-Activated Protein Kinases
Estrogen Receptor alpha
Ovariectomy
Appetite
Puberty
Energy Metabolism
Weight Loss
Down-Regulation
Steroids
Food

Keywords

  • estradiol
  • hypothalamus
  • food intake
  • mTOR
  • obesity

Cite this

González-García, I., Martinez de Morentin, P. B., Estévez-Salguero, Á., Contreras, C., Romero-Picó , A., Fernø, J., ... López, M. (2018). mTOR signaling in the arcuate nucleus of the hypothalamus mediates the anorectic action of estradiol. Journal of Endocrinology, 238(3), 177-186. https://doi.org/10.1530/JOE-18-0190

mTOR signaling in the arcuate nucleus of the hypothalamus mediates the anorectic action of estradiol. / González-García, Ismael; Martinez de Morentin, Pablo B; Estévez-Salguero, Ánxela ; Contreras, Cristina; Romero-Picó , Amparo ; Fernø, Johan; Nogueiras, Ruben; Diéguez, Carlos; Tena-Sempere, Manuel ; Tovar, Sulay; López, Miguel.

In: Journal of Endocrinology, Vol. 238, No. 3, 09.2018, p. 177-186.

Research output: Contribution to journalArticle

González-García, I, Martinez de Morentin, PB, Estévez-Salguero, Á, Contreras, C, Romero-Picó , A, Fernø, J, Nogueiras, R, Diéguez, C, Tena-Sempere, M, Tovar, S & López, M 2018, 'mTOR signaling in the arcuate nucleus of the hypothalamus mediates the anorectic action of estradiol', Journal of Endocrinology, vol. 238, no. 3, pp. 177-186. https://doi.org/10.1530/JOE-18-0190
González-García, Ismael ; Martinez de Morentin, Pablo B ; Estévez-Salguero, Ánxela ; Contreras, Cristina ; Romero-Picó , Amparo ; Fernø, Johan ; Nogueiras, Ruben ; Diéguez, Carlos ; Tena-Sempere, Manuel ; Tovar, Sulay ; López, Miguel. / mTOR signaling in the arcuate nucleus of the hypothalamus mediates the anorectic action of estradiol. In: Journal of Endocrinology. 2018 ; Vol. 238, No. 3. pp. 177-186.
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abstract = "Current evidence suggests that estradiol (E2), the main ovarian steroid, modulates energy balance by regulating both feeding and energy expenditure at the central level, through the energy sensor AMP-activated protein kinase (AMPK). We hypothesized that the hypothalamic mechanistic target of rapamycin (mTOR) pathway, a well-established nutrient sensor and modulator of appetite and puberty, could also mediate the anorectic effect of E2. Our data showed that, ovariectomy (OVX) elicited a marked downregulation of the mTOR signaling in the arcuate nucleus of the hypothalamus (ARC), an effect that was reversed by either E2 replacement or central estrogen receptor alpha (ERα) agonism. The significance of this molecular signaling was given by the genetic inactivation of S6 kinase B1 (S6K1, a key downstream mTOR effector) in the ARC, which prevented the E2-induced hypophagia and weight loss. Overall, these data indicate that E2 induces hypophagia through modulation of mTOR pathway in the ARC",
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AU - Martinez de Morentin, Pablo B

AU - Estévez-Salguero, Ánxela

AU - Contreras, Cristina

AU - Romero-Picó , Amparo

AU - Fernø, Johan

AU - Nogueiras, Ruben

AU - Diéguez, Carlos

AU - Tena-Sempere, Manuel

AU - Tovar, Sulay

AU - López, Miguel

N1 - The authors dedicate this work to the bright memory of our colleague, master and friend Enrique Aguilar. The research leading to these results has received funding from Xunta de Galicia (R N: 2015-CP080 and 2016- PG057; M L: 2015-CP079), Junta de Andalucía (M T-S: P12-FQM-01943), MINECO co-funded by the FEDER Program of EU (C D: BFU2017-87721; R N: BFU2015-70664R; M T-S: BFU2014-57581-P and PIE14/0005; M L: SAF2015- 71026-R and BFU2015-70454-REDT/Adipoplast). The CiMUS is supported by the Xunta de Galicia (2016–2019, ED431G/05). CIBER Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII. A E-S is a recipient of a fellowship from MINECO (FPI/BES-2016-077439). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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N2 - Current evidence suggests that estradiol (E2), the main ovarian steroid, modulates energy balance by regulating both feeding and energy expenditure at the central level, through the energy sensor AMP-activated protein kinase (AMPK). We hypothesized that the hypothalamic mechanistic target of rapamycin (mTOR) pathway, a well-established nutrient sensor and modulator of appetite and puberty, could also mediate the anorectic effect of E2. Our data showed that, ovariectomy (OVX) elicited a marked downregulation of the mTOR signaling in the arcuate nucleus of the hypothalamus (ARC), an effect that was reversed by either E2 replacement or central estrogen receptor alpha (ERα) agonism. The significance of this molecular signaling was given by the genetic inactivation of S6 kinase B1 (S6K1, a key downstream mTOR effector) in the ARC, which prevented the E2-induced hypophagia and weight loss. Overall, these data indicate that E2 induces hypophagia through modulation of mTOR pathway in the ARC

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