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Estrogen receptor–α in medial amygdala neurons regulates body weight
- Publication Year :
- 2015
- Publisher :
- American Society for Clinical Investigation, 2015.
-
Abstract
- 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.
- Subjects :
- Agonist
Male
medicine.medical_specialty
medicine.drug_class
Estrogen receptor
Mice, Transgenic
Biology
Motor Activity
Weight Gain
Amygdala
03 medical and health sciences
Mice
0302 clinical medicine
Glucagon-Like Peptide 1
Internal medicine
medicine
Basic Helix-Loop-Helix Transcription Factors
Animals
Obesity
Receptor
030304 developmental biology
2. Zero hunger
Mice, Knockout
Neurons
0303 health sciences
Sex Characteristics
Corticomedial Nuclear Complex
Body Weight
Estrogen Receptor alpha
food and beverages
Estrogens
General Medicine
Glucagon-like peptide-1
Mice, Inbred C57BL
Repressor Proteins
medicine.anatomical_structure
Endocrinology
SIM1
Commentary
Female
Hypoactivity
Energy Metabolism
Estrogen receptor alpha
030217 neurology & neurosurgery
Signal Transduction
Research Article
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....26b66723f2700aa829b31a3329a9acdb