Department of Physiological Sciences, Institute of Biological Sciences, University of Brasilia, University Campus Darcy Ribeiro, Brasilia, DF 70910-900, Brazil; Graduate Program in Molecular Pathology, Faculty of Health Sciences, University of Brasilia, University Campus Darcy Ribeiro, Brasilia, DF 70910-900, Brazil.
Graduate Program in Biological Sciences: Biochemistry Toxicology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Aug 30;110:110288. doi: 10.1016/j.pnpbp.2021.110288. Epub 2021 Feb 21.
Obesity is a global health problem with high prevalence and defined by a high body mass index (BMI). Several comorbidities affecting the central nervous system (CNS) are associated with obesity (e.g., neurodegenerative diseases, cognitive deficit, and psychobehavioral disturbs). The zebrafish (Danio rerio) has been considered a suitable model organism to investigate the neurobehavioral features of various human diseases. Here, we verify the impact of a high-fat diet (HFD) on the CNS by specifically assessing the effects of short-term HFD on anxiety-like responses, aggression, social preference, and memory, which are essential behaviors for survival and reproduction. Animals were separated in three experimental groups. The standard diet group (SD) received 7.5 mg/fish of dry food, while HFD groups received 5 mg/fish dry food plus 7.5 (HFD-7.5) or 15 mg/fish (HFD-15) of chicken egg yolk daily. Dietary fat content (w/w) was approximately 6.5%, 16.9%, and 21.1%, respectively. We performed behavioral tests and morphometric analyses after two weeks of HFD. In comparison to SD animals, HFD groups showed typical obesogenic responses with increases in BMI, abdominal length, and body weight. HFD individuals also showed increased aggression and anxiety-like behaviors in the mirror-induced aggression and novel tank diving tests, respectively. Interestingly, HFD did not change the social preference behavior, mean swimming speed or spontaneous activity levels, while the HFD-15 group showed cognitive deficits in the inhibitory avoidance test. Collectively, this "proof-of-concept" study is the first report to characterize the effects of short-term HFD on different behavioral domains of zebrafish with high degree of face validity. Moreover, our data reinforce the growing utility of zebrafish to explore the neurobehavioral basis of obesity, providing clinically translatable data, complementing the existing rodent models and supporting future mechanistic studies.
肥胖是一个全球性的健康问题，其患病率很高，定义为身体质量指数（BMI）高。几种影响中枢神经系统（CNS）的合并症与肥胖有关（例如，神经退行性疾病、认知缺陷和心理行为障碍）。斑马鱼（Danio rerio）被认为是一种合适的模式生物，可用于研究各种人类疾病的神经行为特征。在这里，我们通过专门评估短期高脂肪饮食（HFD）对焦虑样反应、攻击性、社会偏好和记忆的影响来验证 CNS 受 HFD 的影响，这些是生存和繁殖的重要行为。动物被分为三组进行实验。标准饮食组（SD）接受 7.5mg/鱼的干饲料，而 HFD 组接受 5mg/鱼的干饲料，外加每天 7.5（HFD-7.5）或 15mg/鱼（HFD-15）的鸡卵黄。饮食脂肪含量（w/w）分别约为 6.5%、16.9%和 21.1%。在 HFD 两周后，我们进行了行为测试和形态计量学分析。与 SD 动物相比，HFD 组表现出典型的肥胖反应，BMI、腹长和体重增加。在镜像诱导攻击和新水箱潜水试验中，HFD 个体也表现出攻击性和焦虑样行为增加。有趣的是，HFD 没有改变社会偏好行为、平均游泳速度或自发活动水平，而 HFD-15 组在抑制回避试验中表现出认知缺陷。总的来说，这项“概念验证”研究是首次报道在具有高度表面效度的情况下，描述短期 HFD 对斑马鱼不同行为领域的影响。此外，我们的数据加强了利用斑马鱼探索肥胖神经行为基础的效用，提供了具有临床转化意义的数据，补充了现有的啮齿动物模型，并支持未来的机制研究。
