Cited by 597Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesEstrogen and related hormone effects

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Distinct Hypothalamic Neurons Mediate Estrogenic Effects on Energy Homeostasis and Reproduction

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Xu, Yong, Nedungadi, Thekkethil P., Zhu, Liangru, Sobhani, Nasim, Irani, Boman G., Davis, Kathryn E., Zhang, Xiaorui, Zou, Fang, Gent, Lana M., Hahner, Lisa D., Khan, Sohaib A., Elias, Carol F., Elmquist, Joel K., Clegg, Deborah J.·2011·Cell Metabolism

DOI 10.1016/j.cmet.2011.08.009PMC PMC3235745

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Abstract

Estrogens regulate body weight and reproduction primarily through actions on estrogen receptor-α (ERα). However, ERα-expressing cells mediating these effects are not identified. We demonstrate that brain-specific deletion of ERα in female mice causes abdominal obesity stemming from both hyperphagia and hypometabolism. Hypometabolism and abdominal obesity, but not hyperphagia, are recapitulated in female mice lacking ERα in hypothalamic steroidogenic factor-1 (SF1) neurons. In contrast, deletion of ERα in hypothalamic pro-opiomelanocortin (POMC) neurons leads to hyperphagia, without directly influencing energy expenditure or fat distribution. Further, simultaneous deletion of ERα from both SF1 and POMC neurons causes hypometabolism, hyperphagia, and increased visceral adiposity. Additionally, female mice lacking ERα in SF1 neurons develop anovulation and infertility, while POMC-specific deletion of ERα inhibits negative feedback regulation of estrogens and impairs fertility in females. These results indicate that estrogens act on distinct hypothalamic ERα neurons to regulate different aspects of energy homeostasis and reproduction.

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Authors: Xu, Y., Nedungadi, T. P., Zhu, L., Sobhani, N., Irani, B. G., Davis, K. E., Zhang, X., Zou, F., Gent, L. M., Hahner, L. D., Khan, S. A., Elias, C. F., Elmquist, J. K., & Clegg, D. J.
Affiliations: Baylor College of Medicine (US)
The University of Texas Southwestern Medical Center (US)
Corresponding author: Clegg, Deborah J.
ORCID: Xu, Yong
Zhu, Liangru
Sobhani, Nasim
Davis, Kathryn E.
Zhang, Xiaorui
Zou, Fang
Elias, Carol F.
Elmquist, Joel K.
Clegg, Deborah J.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2011-10
Volume: 14
Issue: 4
Pages: 453-465
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2011.08.009
PMC: PMC3235745
OpenAlex: W2013865699
Cited by: 597
References: 43
Citations by year: 2026: 19 · 2025: 34 · 2024: 35 · 2023: 36 · 2022: 38 · 2021: 48 · 2020: 42 · 2019: 56 · 2018: 45 · 2017: 54 · 2016: 48 · 2015: 39 · 2014: 36 · 2013: 36 · 2012: 27
FWCI: 14.74
Type: journal article
Language: en
Update notices: erratum (2019-05-07)
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 655 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (DK073689, DK088220, HD061539, P30 DK079638-03, PL1 DK081182, PO1DK088761, R00DK085330, R01DK071320, R01DK088423, R01DK093587, R37DK53301, RL1 DK081185, UL1 RR024923)
American Diabetes Association
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Keywords: estrogen receptor alpha, hypothalamic neurons, energy homeostasis, reproduction, abdominal obesity, hyperphagia, hypometabolism, proopiomelanocortin neurons, anovulation, infertility, estrogen negative feedback, visceral fat, female fertility
MeSH terms: Animals, Energy Metabolism, Estradiol, Female, Hyperphagia, Hypothalamus, Infertility, Female, Male, Neurons, Obesity, Pro-Opiomelanocortin, Mice, Knockout, Estrogen Receptor alpha, Mice, Steroidogenic Factor 1

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Distinct Hypothalamic Neurons Mediate Estrogenic Effects on Energy Homeostasis and Reproduction

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