Backgrounds and aims

Childhood obesity is increasing substantially across the world. The World Obesity Federation (WOF) and World Health Organization (WHO) predicted that in 2030 more than 1 billion people will be obese, and by 2035 over 4 billion will reach obesity worldwide. According to WHO, the world soon cannot afford the economic cost of obesity, and we need to act to stop obesity acceleration now. Data in the literature supports that the first 1000 days of life are essential in preventing obesity and related adversities. Therefore, using basic research, the present a study that focuses on the immediate effect of overnutrition and serotonin modulation during the lactation period.

Methods

Using a neonatal overfeeding model, male Wistar rats were divided into four groups based on nutrition or serotonin modulation by pharmacological treatment up to 22 days of life. Cellular and mitochondrial function markers, oxidative stress biomarkers and mRNA levels of hedonic and homeostatic genes were evaluated.

Results

Our data showed that overfeeding during lactation decrease NAD/NADH ratio, citrate synthase activity, and increase ROS production. Lipid and protein oxidation were increased in overfed animals, with a decrease in antioxidant defenses, we also observe a differential expression of mRNA levels of homeostatic and hedonic genes. On the contrary, serotonin modulation with selective serotonin reuptake inhibitors treatment reduces harmful effects caused by overnutrition.

Conclusion

Early effects of overnutrition significantly affect the prefrontal cortex at molecular and cellular level, which could mediate obesity-related neurodegenerative dysfunction.

中文翻译：

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发育过程中的超重会导致细胞代谢和控制前额皮质食物摄入的关键基因失调

背景和目标

世界各地的儿童肥胖症正在大幅增加。世界肥胖联合会（WOF）和世界卫生组织（WHO）预测，到2030年，全球将有超过10亿人肥胖，到2035年，全球将有超过40亿人肥胖。世界卫生组织表示，世界很快将无法承受肥胖的经济成本，我们现在需要采取行动阻止肥胖加速。文献中的数据表明，生命的前 1000 天对于预防肥胖和相关逆境至关重要。因此，利用基础研究，提出一项研究，重点关注哺乳期营养过剩和血清素调节的直接影响。

方法

使用新生过度喂养模型，将雄性 Wistar 大鼠根据营养或药物治疗的血清素调节分为四组，直至生命 22 天。评估了细胞和线粒体功能标记、氧化应激生物标记以及享乐和稳态基因的 mRNA 水平。

结果

我们的数据表明，哺乳期过度喂养会降低 NAD/NADH 比率、柠檬酸合酶活性，并增加 ROS 产生。过度喂养的动物的脂质和蛋白质氧化增加，抗氧化防御能力下降，我们还观察到稳态和享乐基因的 mRNA 水平的差异表达。相反，通过选择性血清素再摄取抑制剂治疗进行血清素调节可减少营养过剩造成的有害影响。

结论

营养过剩的早期影响在分子和细胞水平上显着影响前额皮质，这可能介导与肥胖相关的神经退行性功能障碍。