Estrogen receptor–α in medial amygdala neurons regulates body weight

Xu, Pingwen; Cao, Xuehong; He, Yanlin; Zhu, Liangru; Yang, Yongjie; Saito, Kenji; Wang, Chunmei; Yan, Xiao; Hinton, Antentor; Zou, Feng-Cai; Ding, Hongfang; Xia, Yan; Yan, Cui‐Wei; Shu, Gang; Wu, San‐Pin; Yang, Bin; Feng, Yi; Clegg, Deborah J.; DeMarchi, Richard; Khan, Sohaib A.; Tsai, Sophia Y.; DeMayo, Francesco J.; Wu, Qi; Tong, Qingchun; Xu, Yong

doi:10.1172/jci80941

Cited by 81 publications

(88 citation statements)

References 51 publications

(60 reference statements)

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“…As we reported previously 26 , SIM1-ERα-KO mice have ERα deleted primarily in the MeA (Figure 1A), with modest deletion in the medial pre-optic area (MPOA, Figure 1B) and the paraventricular nucleus of the hypothalamus (PVN, Figure 1C). Here we used female SIM1-ERα-KO mice and their control (Esr1 f/f ) littermates to examine the role of ERα in SIM1 neurons in the regulation of BP during stress.…”

Section: Resultssupporting

confidence: 79%

“…We have generated a SIM1-ERα-KO (Esr1 f/f /SIM1-Cre) mouse line, in which ERα (encoded by the Esr1 gene) is selectively deleted in single-minded-1 (SIM1) neurons 26 . As we reported previously 26 , SIM1-ERα-KO mice have ERα deleted primarily in the MeA (Figure 1A), with modest deletion in the medial pre-optic area (MPOA, Figure 1B) and the paraventricular nucleus of the hypothalamus (PVN, Figure 1C).…”

Section: Resultsmentioning

confidence: 99%

“…Brain sections were collected and subjected to mCherry immunohistochemistry, as described before 26 . Briefly, brain sections were first incubated in 0.3% H 2 O 2 in PBS for 30 minutes to abolish endogenous peroxidase activity.…”

Section: Methodsmentioning

confidence: 99%

“…As we described before 26, 27 , six to twelve week old female mice were deeply anesthetized with isoflurane and transcardially perfused with a modified ice-cold sucrose-based cutting solution (adjusted to pH 7.3) containing (in mM) 10 NaCl, 25 NaHCO 3 , 195 Sucrose, 5 Glucose, 2.5 KCl, 1.25 NaH 2 PO 4 , 2 Na pyruvate, 0.5 CaCl 2 , 7 MgCl 2 bubbled continuously with 95% O 2 and 5% CO 2 . The mice were then decapitated, and the entire brain was removed and immediately submerged in ice-cold sucrose-based cutting solution.…”

Section: Methodsmentioning

confidence: 99%

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Estrogen Receptor-α in the Medial Amygdala Prevents Stress-Induced Elevations in Blood Pressure in Females

Hinton

Xia

et al. 2016

Hypertension

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Psychological stress contributes to the development of hypertension in humans. The ovarian hormone, estrogen, has been shown to prevent stress-induced pressor responses in females by unknown mechanisms. Here we showed that the anti-hypertensive effects of estrogen during stress were blunted in female mice lacking estrogen receptor-α (ERα) in the brain medial amygdala (MeA). Deletion of ERα in MeA neurons also resulted in increased excitability of these neurons, associated with elevated ionotropic glutamate receptor expression. We further demonstrated that selective activation of MeA neurons mimicked effects of stress to increase blood pressure in mice. Together, our results support a model where estrogen acts upon ERα expressed by MeA neurons to prevent stress-induced activation of these neurons, and therefore prevents pressor responses to stress.

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Section: Resultssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Estrogen Receptor-α in the Medial Amygdala Prevents Stress-Induced Elevations in Blood Pressure in Females

Hinton

Xia

et al. 2016

Hypertension

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“…Recent efforts in the field have led to an appreciation that estrogenic actions on different aspects of energy balance are mediated by distinct ERα neural populations in the brain. For example, the inhibitory effects of 17β-estradiol on food intake are mediated by ERα expressed in the arcuate hypothalamic nucleus (ARH) [12], the dorsal nucleus raphe (DR) [13] and the nucleus of the solitary tract (NTS) [14]; ERα in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH), however, mediates estrogenic actions to enhance energy expenditure but does not affect feeding [12, 15–17]; ERα in the medial amygdalar nucleus (MeA) is functionally required to maintain normal physical activity [18]. …”

Section: Introductionmentioning

confidence: 99%

Visualizing estrogen receptor-α-expressing neurons using a new ERα-ZsGreen reporter mouse line

Saito

Yan

et al. 2016

Metabolism

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Background A variety of biological functions of estrogens, including regulation of energy metabolism, are mediated by neurons expressing estrogen receptor-α (ERα) in the brain. However, complex intracellular processes in these ERα-expressing neurons are difficult to unravel, due to the lack of strategy to visualize ERα-expressing neurons, especially in unfixed brain tissues. Results and Conclusions Here we generated a novel ERα-ZsGreen reporter mouse line in which expression of a green fluorescent reporter protein, ZsGreen, is driven by a 241 kb ERα gene promoter. We validated that ZsGreen is highly colocalized with endogenous ERα in the brain. Native ZsGreen signals were visualized in unfixed brain tissue, and were used to assist single cell collection and electrophysiological recordings. Finally, we demonstrated that this ERα-ZsGreen mouse allele can be used in combination with other genetic reporter alleles to allow experiments in highly selective neural populations.

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Brown and Beige Adipose Tissues in Health and Disease

Rui

2017

Comprehensive Physiology

136

103

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Brown and beige adipocytes arise from distinct developmental origins. Brown adipose tissue (BAT) develops embryonically from precursors that also give to skeletal muscle. Beige fat develops postnatally and is highly inducible. Beige fat recruitment is mediated by multiple mechanisms, including de novo beige adipogenesis and white-to-brown adipocyte transdifferentiaiton. Beige precursors reside around vasculatures, and proliferate and differentiate into beige adipocytes. PDGFRα+Ebf2+ precursors are restricted to beige lineage cells, while another PDGFRα+ subset gives rise to beige adipocytes, white adipocytes, or fibrogenic cells. White adipocytes can be reprogramed and transdifferentiated into beige adipocytes. Brown and beige adipocytes display many similar properties, including multilocular lipid droplets, dense mitochondria, and expression of UCP1. UCP1-mediated thermogenesis is a hallmark of brown/beige adipocytes, albeit UCP1-independent thermogenesis also occurs. Development, maintenance, and activation of BAT/beige fat are guided by genetic and epigenetic programs. Numerous transcriptional factors and coactivators act coordinately to promote BAT/beige fat thermogenesis. Epigenetic reprograming also influences expression of brown/beige adipocyte-selective genes. BAT/beige fat is regulated by neuronal, hormonal, and immune mechanisms. Hypothalamic thermal circuits define the temperature setpoint that guides BAT/beige fat activity. Metabolic hormones, paracrine/autocrine factors, and various immune cells also play a critical role in regulating BAT/beige fat functions. BAT and beige fat defend temperature homeostasis, and regulate body weight and glucose and lipid metabolism. Obesity is associated with brown/beige fat deficiency, and reactivation of brown/beige fat provides metabolic health benefits in some patients. Pharmacological activation of BAT/beige fat may hold promise for combating metabolic diseases.

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Estrogen receptor–α in medial amygdala neurons regulates body weight

Cited by 81 publications

References 51 publications

Estrogen Receptor-α in the Medial Amygdala Prevents Stress-Induced Elevations in Blood Pressure in Females

Estrogen Receptor-α in the Medial Amygdala Prevents Stress-Induced Elevations in Blood Pressure in Females

Visualizing estrogen receptor-α-expressing neurons using a new ERα-ZsGreen reporter mouse line

Brown and Beige Adipose Tissues in Health and Disease

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