TY - JOUR
T1 - mTOR signaling in the arcuate nucleus of the hypothalamus mediates the anorectic action of estradiol
AU - González-García, Ismael
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.
PY - 2018/9
Y1 - 2018/9
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
AB - 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
KW - estradiol
KW - hypothalamus
KW - food intake
KW - mTOR
KW - obesity
U2 - 10.1530/JOE-18-0190
DO - 10.1530/JOE-18-0190
M3 - Article
VL - 238
SP - 177
EP - 186
JO - Journal of Endocrinology
JF - Journal of Endocrinology
SN - 0022-0795
IS - 3
ER -
