Dataset Information

RLN3/RXFP3 Signaling in the PVN Inhibits Magnocellular Neurons via M-like Current Activation and Contributes to Binge Eating Behavior.

ABSTRACT: Binge-eating disorder is the most common eating disorder. Various neuropeptides play important roles in the regulation of feeding behavior, including relaxin-3 (RLN3), which stimulates food intake in rats through the activation of the relaxin-family peptide-3 receptor (RXFP3). Here we demonstrate that a likely mechanism underlying the orexigenic action of RLN3 is RXFP3-mediated inhibition of oxytocin- and arginine-vasopressin-synthesizing paraventricular nucleus (PVN) magnocellular neurosecretory cells. Moreover, we reveal that, in male and female rats, this action depends on M-like potassium conductance. Notably, higher intra- and peri-PVN RLN3 fiber densities were observed in females, which may constitute an anatomic substrate for observed sex differences in binge-eating disorder. Finally, in a model of binge-eating in female rats, RXFP3 blockade within the PVN prevented binge-eating behavior. These data demonstrate a direct RLN3/RXFP3 action in the PVN of male and female rats, identify the associated ionic mechanisms, and reveal that hypothalamic RLN3/RXFP3 signaling regulates binge-eating behavior.SIGNIFICANCE STATEMENT Binge-eating disorder is the most common eating disorder worldwide, affecting women twice as frequently as men. Various neuropeptides play important roles in the regulation of feeding behavior, including relaxin-3, which acts via the relaxin-family peptide-3 receptor (RXFP3). Using a model of binge-eating, we demonstrated that relaxin-3/RXFP3 signaling in the hypothalamic paraventricular nucleus (PVN) is necessary for the expression of binge-eating behavior in female rats. Moreover, we elucidated the neuronal mechanism of RLN3/RXFP3 signaling in PVN in male and female rats and characterized sex differences in the RLN3 innervation of the PVN. These findings increase our understanding of the brain circuits and neurotransmitters involved in binge-eating disorder pathology and identify RXFP3 as a therapeutic target for binge-like eating disorders.

SUBMITTER: Kania A

PROVIDER: S-EPMC7343322 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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RLN3/RXFP3 Signaling in the PVN Inhibits Magnocellular Neurons via M-like Current Activation and Contributes to Binge Eating Behavior.

Kania Alan A Szlaga Agata A Sambak Patryk P Gugula Anna A Blasiak Ewa E Micioni Di Bonaventura Maria Vittoria MV Hossain Mohammad Akhter MA Cifani Carlo C Hess Grzegorz G Gundlach Andrew L AL Blasiak Anna A

The Journal of neuroscience : the official journal of the Society for Neuroscience 20200612 28

Binge-eating disorder is the most common eating disorder. Various neuropeptides play important roles in the regulation of feeding behavior, including relaxin-3 (RLN3), which stimulates food intake in rats through the activation of the relaxin-family peptide-3 receptor (RXFP3). Here we demonstrate that a likely mechanism underlying the orexigenic action of RLN3 is RXFP3-mediated inhibition of oxytocin- and arginine-vasopressin-synthesizing paraventricular nucleus (PVN) magnocellular neurosecretor ...[more]

PMID: 32532885

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Project description:BackgroundCurrent guidelines recommend cognitive behavior therapy (CBT) as the treatment of choice for binge eating disorder (BED). Although CBT is quite effective, a substantial number of patients do not reach abstinence from binge eating. To tackle this problem, various theoretical conceptualizations and treatment models have been proposed. Dialectical behavior therapy (DBT), focusing on emotion regulation, is one such model. Preliminary evidence comparing DBT adapted for BED (DBT-BED) to CBT is promising but the available data do not favor one treatment over the other. The aim of this study is to evaluate outcome of DBT-BED, compared to a more intensive eating disorders-focused form of cognitive behavior therapy (CBT+), in individuals with BED who are overweight and engage in emotional eating.MethodsSeventy-four obese patients with BED who reported above average levels of emotional eating were quasi-randomly allocated to one of two manualized 20-session group treatments: DBT-BED (n = 41) or CBT+ (n = 33). Intention-to-treat outcome was examined at post-treatment and at 6-month follow-up using general or generalized linear models with multiple imputation.ResultsOverall, greater improvements were observed in CBT+. Differences in number of objective binge eating episodes at end of treatment, and eating disorder psychopathology (EDE-Q Global score) and self-esteem (EDI-3 Low Self-Esteem) at follow-up reached statistical significance with medium effect sizes (Cohen's d between .46 and .59). Of the patients in the DBT group, 69.9% reached clinically significant change at end of the treatment vs 65.0% at follow-up. Although higher, this was not significantly different from the patients in the CBT+ group (52.9% vs 45.8%).ConclusionsThe results of this study show that CBT+ produces better outcomes than the less intensive DBT-BED on several measures. Yet, regardless of the dose-difference, the data suggest that DBT-BED and CBT+ lead to comparable levels of clinically meaningful change in global eating disorder psychopathology. Future recommendations include the need for dose-matched comparisons in a sufficiently powered randomized controlled trial, and the need to determine mediators and moderators of treatment outcome.Trial registrationNederlands Trial Register: NL3982 (NTR4154). Date of registration: 2013 August 28, retrospectively registered.

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.

Dataset Information

RLN3/RXFP3 Signaling in the PVN Inhibits Magnocellular Neurons via M-like Current Activation and Contributes to Binge Eating Behavior.

Publications

RLN3/RXFP3 Signaling in the PVN Inhibits Magnocellular Neurons via M-like Current Activation and Contributes to Binge Eating Behavior.

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