Júnior Renato Elias Moreira, Pedersen Agatha Sondertoft Braga, Ferreira Raquel Mary, de Asevedo Guilherme Henrique, Mendes Grazielle Laudares, Ribeiro Karine, Maioli Tatiani Uceli, de Faria Ana Maria Caetano, Brunialti-Godard Ana Lúcia
Laboratório de Genética Animal e Humana, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Laboratório de Genética Animal e Humana, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
J Nutr Biochem. 2025 Jan;135:109784. doi: 10.1016/j.jnutbio.2024.109784. Epub 2024 Oct 18.
Binge Eating Disorder (BED) is among the most prevalent eating disorders worldwide. It is characterized by recurrent episodes of excessive consumption of palatable foods in short periods, accompanied by a sense of loss of control and distress around the episode, which tends to worsen over time. The mesolimbic dopaminergic system influences on reinforcement and reward-seeking behaviors is implicated in the disorder's pathogenesis. Animal models that replicate the clinical conditions observed in humans, including the disorder progression, are essential for understanding the underlying physiological mechanisms of BED. This study aimed to evaluate binge eating behavior induced by intermittent High Sugar and Butter (HSB) diet access in mice, their phenotypes, transcriptional regulation of mesolimbic dopaminergic system genes, and behavior. Thus, mice were subdivided into three groups: CHOW (maintenance diet only), HSB-i (maintenance diet with thrice-weekly access to HSB), and HSB (continuous access to HSB). Animals were subjected to marble-burying and light-dark box behavioral tests, and transcriptional regulation was evaluated by RT-qPCR. The results indicated that the HSB-i group established a feeding pattern of significantly more kilocalories on days when HSB was available and reduced intake on non-HSB days similar to human binge eating. Over time, binge episodes intensified, potentially indicating a tolerance effect. Additionally, these animals behave differently towards preferring the HSB diet and exhibited altered transcriptional regulation of the Drd1, Slc6a3, and Lrrk2 genes. Our study provides a mouse model that reflects human BED, showing a progression in binge episodes and mesolimbic dopamine pathway involvement, suggesting targets for future therapeutic interventions.
暴饮暴食症（BED）是全球最普遍的饮食失调症之一。其特征是在短时间内反复出现过度食用美味食物的情况，同时伴有失控感和围绕该发作的痛苦，且这种情况往往会随着时间的推移而恶化。中脑边缘多巴胺能系统对强化和寻求奖励行为的影响与该疾病的发病机制有关。能够复制人类观察到的临床状况（包括疾病进展）的动物模型，对于理解BED的潜在生理机制至关重要。本研究旨在评估间歇性高糖和黄油（HSB）饮食对小鼠诱发的暴饮暴食行为、它们的表型、中脑边缘多巴胺能系统基因的转录调控以及行为。因此，将小鼠分为三组：CHOW组（仅维持饮食）、HSB-i组（维持饮食并每周三次给予HSB）和HSB组（持续给予HSB）。对动物进行埋珠和明暗箱行为测试，并通过RT-qPCR评估转录调控。结果表明，HSB-i组在可获得HSB的日子里建立了显著更多千卡的进食模式，而在非HSB日摄入量减少，类似于人类的暴饮暴食。随着时间的推移，暴饮暴食发作加剧，这可能表明存在耐受效应。此外，这些动物对HSB饮食的偏好行为不同，并且Drd1、Slc6a3和Lrrk2基因的转录调控发生了改变。我们的研究提供了一个反映人类BED的小鼠模型，显示出暴饮暴食发作的进展以及中脑边缘多巴胺途径的参与，为未来的治疗干预提供了靶点。
