PMID- 29914932
OWN - NLM
STAT- MEDLINE
DCOM- 20190820
LR  - 20211204
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 238
IP  - 3
DP  - 2018 Sep
TI  - mTOR signaling in the arcuate nucleus of the hypothalamus mediates the anorectic 
      action of estradiol.
PG  - 177-186
LID - 10.1530/JOE-18-0190 [doi]
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 (ERalpha) 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.
CI  - (c) 2018 The authors.
FAU - Gonzalez-Garcia, Ismael
AU  - Gonzalez-Garcia I
AD  - Department of PhysiologyCiMUS, University of Santiago de Compostela-Instituto de 
      Investigacion Sanitaria, Santiago de Compostela, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Santiago de Compostela, 
      Spain.
FAU - Martinez de Morentin, Pablo B
AU  - Martinez de Morentin PB
AD  - Department of PhysiologyCiMUS, University of Santiago de Compostela-Instituto de 
      Investigacion Sanitaria, Santiago de Compostela, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Santiago de Compostela, 
      Spain.
FAU - Estevez-Salguero, Anxela
AU  - Estevez-Salguero A
AD  - Department of PhysiologyCiMUS, University of Santiago de Compostela-Instituto de 
      Investigacion Sanitaria, Santiago de Compostela, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Santiago de Compostela, 
      Spain.
FAU - Contreras, Cristina
AU  - Contreras C
AD  - Department of PhysiologyCiMUS, University of Santiago de Compostela-Instituto de 
      Investigacion Sanitaria, Santiago de Compostela, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Santiago de Compostela, 
      Spain.
FAU - Romero-Pico, Amparo
AU  - Romero-Pico A
AD  - Department of PhysiologyCiMUS, University of Santiago de Compostela-Instituto de 
      Investigacion Sanitaria, Santiago de Compostela, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Santiago de Compostela, 
      Spain.
FAU - Ferno, Johan
AU  - Ferno J
AD  - Hormone LaboratoryHaukeland University Hospital, Bergen, Norway.
AD  - KG Jebsen Center for Diabetes ResearchDepartment of Clinical Science, University 
      of Bergen, Bergen, Norway.
FAU - Nogueiras, Ruben
AU  - Nogueiras R
AD  - Department of PhysiologyCiMUS, University of Santiago de Compostela-Instituto de 
      Investigacion Sanitaria, Santiago de Compostela, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Santiago de Compostela, 
      Spain.
FAU - Dieguez, Carlos
AU  - Dieguez C
AD  - Department of PhysiologyCiMUS, University of Santiago de Compostela-Instituto de 
      Investigacion Sanitaria, Santiago de Compostela, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Santiago de Compostela, 
      Spain.
FAU - Tena-Sempere, Manuel
AU  - Tena-Sempere M
AD  - Department of Cell BiologyPhysiology and Immunology, University of Cordoba, 
      Cordoba, Spain.
AD  - Instituto Maimonides de Investigacion Biomedica (IMIBIC)/Hospital Reina 
      SofiaCordoba, Spain.
AD  - FiDiPro ProgramUniversity of Turku, Turku, Finland.
FAU - Tovar, Sulay
AU  - Tovar S
AD  - Department of PhysiologyCiMUS, University of Santiago de Compostela-Instituto de 
      Investigacion Sanitaria, Santiago de Compostela, Spain sulay.tovar@usc.es 
      m.lopez@usc.es.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Santiago de Compostela, 
      Spain.
FAU - Lopez, Miguel
AU  - Lopez M
AD  - Department of PhysiologyCiMUS, University of Santiago de Compostela-Instituto de 
      Investigacion Sanitaria, Santiago de Compostela, Spain sulay.tovar@usc.es 
      m.lopez@usc.es.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Santiago de Compostela, 
      Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180618
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Appetite Depressants)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
MH  - Animals
MH  - Anorexia/*chemically induced/*metabolism
MH  - Appetite Depressants/pharmacology
MH  - Arcuate Nucleus of Hypothalamus/*drug effects/metabolism
MH  - Body Weight/drug effects
MH  - Eating/drug effects/physiology
MH  - Estradiol/*pharmacology
MH  - Female
MH  - Ovariectomy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/physiology
MH  - TOR Serine-Threonine Kinases/*metabolism/physiology
PMC - PMC6055430
OTO - NOTNLM
OT  - estradiol
OT  - food intake
OT  - hypothalamus
OT  - mTOR
OT  - obesity
EDAT- 2018/06/20 06:00
MHDA- 2019/08/21 06:00
PMCR- 2018/07/23
CRDT- 2018/06/20 06:00
PHST- 2018/06/11 00:00 [received]
PHST- 2018/06/18 00:00 [accepted]
PHST- 2018/06/20 06:00 [pubmed]
PHST- 2019/08/21 06:00 [medline]
PHST- 2018/06/20 06:00 [entrez]
PHST- 2018/07/23 00:00 [pmc-release]
AID - JOE-18-0190 [pii]
AID - JOE180190 [pii]
AID - 10.1530/JOE-18-0190 [doi]
PST - ppublish
SO  - J Endocrinol. 2018 Sep;238(3):177-186. doi: 10.1530/JOE-18-0190. Epub 2018 Jun 
      18.