RT Journal Article
T1 Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress.
A1 Gonzalez-Garcia, Ismael
A1 Contreras, Cristina
A1 Estevez-Salguero, Anxela
A1 Ruiz-Pino, Francisco
A1 Colsh, Benoit
A1 Pensado, Ivan
A1 Liñares-Pose, Laura
A1 Rial-Pensado, Eva
A1 Martinez de Morentin, Pablo B
A1 Fernø, Johan
A1 Dieguez, Carlos
A1 Nogueiras, Ruben
A1 Le Stunff, Herve
A1 Magnan, Christophe
A1 Tena-Sempere, Manuel
A1 Lopez, Miguel
K1 Brown adipose tissue
K1 Ceramides
K1 Endoplasmic reticulum stress
K1 Estradiol
K1 Hypothalamus
K1 Thermogenesis
AB 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.
PB Cell Press
YR 2018
FD 2018-09-11
LK http://hdl.handle.net/10668/13056
UL http://hdl.handle.net/10668/13056
LA en
NO González-García I, Contreras C, Estévez-Salguero Á, Ruíz-Pino F, Colsh B, Pensado I, et al. Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress. Cell Rep. 2018 Oct 9;25(2):413-423.e5
NO We dedicate this work to the bright memory of our colleague, master, andfriend Enrique Aguilar. The research leading to these results received fundingfrom the European Community’s Seventh Framework Programme (FP7/2007-2013) for the ObERStress European Research Council Project (281854 toM.L.), Xunta de Galicia (EM 2012/039 and 2012-CP069 to R.N.; 2015-CP079to M.L.), Junta de Andalucı´a (P12-FQM-01943 to M.T.-S.), MINECO, whichwas co-funded by the FEDER Program of EU (BFU2011-29102 to C.D.;BFU2012-35255 to R.N.; BFU2014-57581-P to M.T.-S.; SAF2015-71026-Rand BFU2015-70454-REDT/Adipoplast to M.L.), and the Stiftelsen KristianGerhard Jebsen and Western Norway Regional Health Authority (to J.F.).I.G.-G. received a fellowship from MINECO (FPU12/01827); C.C. received aSara Borrell Contract from ISCIII (CD14/0007); A.E.-S. received a fellowshipfrom MINECO (FPI/BES-2016-077439); L.L.-P. received a fellowship fromXunta de Galicia (ED481A-2016/094); and E.R.-P. received a fellowship fromMINECO (FPI/BES-2015-072743). The CiMUS is supported by the Xunta deGalicia (2016-2019, ED431G/05). CIBER de Fisiopatologı´a de la Obesidad yNutricio´ n is an initiative of ISCIII. The funders had no role in study design,data collection and analysis, decision to publish, or preparation of themanuscript.
DS RISalud
RD Apr 9, 2025