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Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice.

ABSTRACT: Binge eating afflicts approximately 5% of US adults, though effective treatments are limited. Here, we showed that estrogen replacement substantially suppresses binge-like eating behavior in ovariectomized female mice. Estrogen-dependent inhibition of binge-like eating was blocked in female mice specifically lacking estrogen receptor-? (ER?) in serotonin (5-HT) neurons in the dorsal raphe nuclei (DRN). Administration of a recently developed glucagon-like peptide-1-estrogen (GLP-1-estrogen) conjugate designed to deliver estrogen to GLP1 receptor-enhanced regions effectively targeted bioactive estrogens to the DRN and substantially suppressed binge-like eating in ovariectomized female mice. Administration of GLP-1 alone reduced binge-like eating, but not to the same extent as the GLP-1-estrogen conjugate. Administration of ER?-selective agonist propylpyrazole triol (PPT) to murine DRN 5-HT neurons activated these neurons in an ER?-dependent manner. PPT also inhibited a small conductance Ca2+-activated K+ (SK) current; blockade of the SK current prevented PPT-induced activation of DRN 5-HT neurons. Furthermore, local inhibition of the SK current in the DRN markedly suppressed binge-like eating in female mice. Together, our data indicate that estrogens act upon ER? to inhibit the SK current in DRN 5-HT neurons, thereby activating these neurons to suppress binge-like eating behavior and suggest ER? and/or SK current in DRN 5-HT neurons as potential targets for anti-binge therapies.

SUBMITTER: Cao X

PROVIDER: S-EPMC4191033 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice.

Cao Xuehong X Xu Pingwen P Oyola Mario G MG Xia Yan Y Yan Xiaofeng X Saito Kenji K Zou Fang F Wang Chunmei C Yang Yongjie Y Hinton Antentor A Yan Chunling C Ding Hongfang H Zhu Liangru L Yu Likai L Yang Bin B Feng Yuxin Y Clegg Deborah J DJ Khan Sohaib S DiMarchi Richard R Mani Shaila K SK Tong Qingchun Q Xu Yong Y

The Journal of clinical investigation 20140826 10

Binge eating afflicts approximately 5% of US adults, though effective treatments are limited. Here, we showed that estrogen replacement substantially suppresses binge-like eating behavior in ovariectomized female mice. Estrogen-dependent inhibition of binge-like eating was blocked in female mice specifically lacking estrogen receptor-α (ERα) in serotonin (5-HT) neurons in the dorsal raphe nuclei (DRN). Administration of a recently developed glucagon-like peptide-1-estrogen (GLP-1-estrogen) conju ...[more]

PMID: 25157819

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Project description:ObjectiveAlthough several effective behavioral treatments for binge-eating disorder (BED) exist, there are racial disparities in treatment access, with African-Americans and/or Black individuals having some of the lowest rates of access to care. Little is known about the experience and treatment of binge eating (BE) and BED among Black women.MethodThis systematic review, conducted according to PRISMA guidelines, synthesizes information related to BE and BED in Black women.ResultsA total of N = 38 studies met our eligibility criteria. We did not identify any systematic risk of bias across studies. The majority of included studies used cross-sectional survey methodology, and relied on interview (EDE) and self-report measures (particularly the Binge Eating Scale, BES) for the assessment of BE. Outcomes were inconsistently measured across trials, and there are limited data on the results of evidence-based treatments for BE/BED in Black women.DiscussionAlthough Black women have similar or higher rates of BE than White women, most research on BE and BED has focused on White women, with Black individuals underrepresented in clinical trials. Future research should examine evidence-based treatments to prevent and treat BED in this population.ObjetivoAunque existen varios tratamientos conductuales que son efectivos para el Trastorno de Atracones (BED, por sus siglas en inglés), existen disparidades raciales en el acceso a tratamiento, con individuos Afroamericanos y/o personas de color teniendo algunas de las tasas más bajas de acceso al cuidado de la salud. Se sabe muy poco acerca de la experiencia y tratamiento del comer en atracones (BE, por sus siglas en inglés) y BED entre mujeres afroamericanas y/o de color. MÉTODO: Esta revisión sistemática, realizada bajo lineamientos de las guías PRISMA, sintetiza información relacionada con BE y BED en mujeres afroamericanas y/o de color.ResultadosUn total de N = 38 estudios cumplieron con nuestros criterios de elegibilidad. No identificamos ningún riesgo sistemático de sesgo entre los estudios. La mayoría de los estudios incluidos utilizaron una metodología de encuesta transversal y se basaron en la entrevista (EDE) y las medidas de autoinforme (en particular, la Binge Eating Scale, BES) para la evaluación de BE. Los resultados se midieron de manera inconsistente entre los ensayos, y hay datos limitados sobre los resultados de los tratamientos basados en la evidencia para BE/BED en mujeres afroamericanas y/o de color. DISCUSIÓN: Aunque las mujeres afroamericanas y/o de color tienen tasas similares o más altas de BE que las mujeres blancas, la mayoría de las investigaciones sobre BE y BED se han centrado en las mujeres blancas, con individuos afroamericanos y/o de color subrepresentados en ensayos clínicos. La investigación futura debería examinar los tratamientos basados en la evidencia para prevenir y tratar el BED en esta población.

Project description:Binge eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell ("frustration stress"). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg-1) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior.

Dataset Information

Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice.

Publications

Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice.

Similar Datasets

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