Zhang Qin, Jin Kangyu, Chen Bing, Liu Ripeng, Cheng Shangping, Zhang Yuyan, Lu Jing
First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Neurosci. 2022 Jul 6;16:884579. doi: 10.3389/fnins.2022.884579. eCollection 2022.
Overnutrition-related obesity has become a worldwide epidemic, and its prevalence is expected to steadily rise in the future. It is widely recognized that obesity exerts negative impacts on metabolic disorders such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases. However, relatively fewer reports exist on the impairment of brain structure and function, in the form of memory and executive dysfunction, as well as neurogenerative diseases. Emerging evidence indicates that besides obesity, overnutrition diets independently induce cognitive impairments multiple mechanisms. In this study, we reviewed the clinical and preclinical literature about the detrimental effects of obesity or high-nutrition diets on cognitive performance and cerebral structure. We mainly focused on the role of brain insulin resistance (IR), microbiota-gut-brain axis, and neuroinflammation. We concluded that before the onset of obesity, short-term exposure to high-nutrition diets already blunted central responses to insulin, altered gut microbiome composition, and activated inflammatory mediators. Overnutrition is linked with the changes in protein expression in brain insulin signaling, leading to pathological features in the brain. Microbiome alteration, bacterial endotoxin release, and gut barrier hyperpermeability also occur to trigger mental and neuronal diseases. In addition, obesity or high-nutrition diets cause chronic and low-grade systematic inflammation, which eventually spreads from the peripheral tissue to the central nervous system (CNS). Altogether, a large number of unknown but potential routes interact and contribute to obesity or diet-induced cognitive impairment. The challenge for future research is to identify effective interventions involving dietary shifts and personalized therapy targeting the underlying mechanisms to prevent and improve cognition deficits.
与营养过剩相关的肥胖已成为一种全球流行病，预计其患病率在未来还将稳步上升。人们普遍认识到，肥胖会对2型糖尿病（T2DM）和心血管疾病等代谢紊乱产生负面影响。然而，关于以记忆和执行功能障碍以及神经退行性疾病形式出现的脑结构和功能损害的报道相对较少。新出现的证据表明，除了肥胖之外，营养过剩饮食会通过多种机制独立诱发认知障碍。在本研究中，我们回顾了关于肥胖或高营养饮食对认知表现和脑结构有害影响的临床和临床前文献。我们主要关注脑胰岛素抵抗（IR）、微生物群-肠-脑轴和神经炎症的作用。我们得出的结论是，在肥胖发生之前，短期接触高营养饮食就已经削弱了中枢对胰岛素的反应，改变了肠道微生物群组成，并激活了炎症介质。营养过剩与脑胰岛素信号通路中蛋白质表达的变化有关，导致大脑出现病理特征。微生物群改变、细菌内毒素释放和肠道屏障通透性增加也会引发精神和神经疾病。此外，肥胖或高营养饮食会导致慢性低度全身炎症，最终从外周组织扩散到中枢神经系统（CNS）。总之，大量未知但潜在的途径相互作用，导致肥胖或饮食诱导的认知障碍。未来研究的挑战是确定有效的干预措施，包括饮食调整和针对潜在机制的个性化治疗，以预防和改善认知缺陷。
