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Tytuł pozycji:

Estrogen receptor-α in medial amygdala neurons regulates body weight.

Tytuł:
Estrogen receptor-α in medial amygdala neurons regulates body weight.
Autorzy:
Xu P
Cao X
He Y
Zhu L
Yang Y
Saito K
Wang C
Yan X
Hinton AO Jr
Zou F
Ding H
Xia Y
Yan C
Shu G
Wu SP
Yang B
Feng Y
Clegg DJ
DeMarchi R
Khan SA
Tsai SY
DeMayo FJ
Wu Q
Tong Q
Xu Y
Źródło:
The Journal of clinical investigation [J Clin Invest] 2015 Jul 01; Vol. 125 (7), pp. 2861-76. Date of Electronic Publication: 2015 Jun 22.
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
MeSH Terms:
Body Weight/*physiology
Corticomedial Nuclear Complex/*metabolism
Estrogen Receptor alpha/*metabolism
Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Corticomedial Nuclear Complex/cytology ; Corticomedial Nuclear Complex/drug effects ; Energy Metabolism ; Estrogen Receptor alpha/deficiency ; Estrogen Receptor alpha/genetics ; Estrogens/administration & dosage ; Female ; Glucagon-Like Peptide 1/administration & dosage ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Motor Activity/physiology ; Neurons/metabolism ; Obesity/etiology ; Obesity/metabolism ; Obesity/pathology ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Sex Characteristics ; Signal Transduction ; Weight Gain/physiology
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Grant Information:
T32CA059268 United States CA NCI NIH HHS; T32 CA059268 United States CA NCI NIH HHS; U54 HD083092 United States HD NICHD NIH HHS; U19 DK062434 United States DK NIDDK NIH HHS; P30 HD024064 United States HD NICHD NIH HHS; R56 DK109194 United States DK NIDDK NIH HHS; R25 GM056929 United States GM NIGMS NIH HHS; DK5U19DK062434 United States DK NIDDK NIH HHS; R01 DK093587 United States DK NIDDK NIH HHS; P30HD024064 United States HD NICHD NIH HHS; R00DK085330 United States DK NIDDK NIH HHS; R01 DK092605 United States DK NIDDK NIH HHS; DK59820 United States DK NIDDK NIH HHS; R01DK092605 United States DK NIDDK NIH HHS; R01DK101379 United States DK NIDDK NIH HHS; P01 DK088761 United States DK NIDDK NIH HHS; R01DK093587 United States DK NIDDK NIH HHS; R00 DK085330 United States DK NIDDK NIH HHS; R01 DK101379 United States DK NIDDK NIH HHS
Substance Nomenclature:
0 (Basic Helix-Loop-Helix Transcription Factors)
0 (Estrogen Receptor alpha)
0 (Estrogens)
0 (Repressor Proteins)
0 (Sim1 protein, mouse)
89750-14-1 (Glucagon-Like Peptide 1)
Entry Date(s):
Date Created: 20150623 Date Completed: 20150916 Latest Revision: 20201112
Update Code:
20240104
PubMed Central ID:
PMC4563687
DOI:
10.1172/JCI80941
PMID:
26098212
Czasopismo naukowe
Estrogen receptor-α (ERα) activity in the brain prevents obesity in both males and females. However, the ERα-expressing neural populations that regulate body weight remain to be fully elucidated. Here we showed that single-minded-1 (SIM1) neurons in the medial amygdala (MeA) express abundant levels of ERα. Specific deletion of the gene encoding ERα (Esr1) from SIM1 neurons, which are mostly within the MeA, caused hypoactivity and obesity in both male and female mice fed with regular chow, increased susceptibility to diet-induced obesity (DIO) in males but not in females, and blunted the body weight-lowering effects of a glucagon-like peptide-1-estrogen (GLP-1-estrogen) conjugate. Furthermore, selective adeno-associated virus-mediated deletion of Esr1 in the MeA of adult male mice produced a rapid body weight gain that was associated with remarkable reductions in physical activity but did not alter food intake. Conversely, overexpression of ERα in the MeA markedly reduced the severity of DIO in male mice. Finally, an ERα agonist depolarized MeA SIM1 neurons and increased their firing rate, and designer receptors exclusively activated by designer drug-mediated (DREADD-mediated) activation of these neurons increased physical activity in mice. Collectively, our results support a model where ERα signals activate MeA neurons to stimulate physical activity, which in turn prevents body weight gain.
Comment in: J Clin Invest. 2015 Jul 1;125(7):2576-8. (PMID: 26098209)

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