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

Keywords

  • estradiol
  • hypothalamus
  • food intake
  • mTOR
  • obesity

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