肥胖引起的胰岛素抵抗对认知障碍的影响机制研究进展

Research Advances in the Mechanism of Obesity-induced Insulin Resistance on Cognitive Impairment

肥胖是引起胰岛素抵抗的主要原因,胰岛素抵抗又是大脑认知障碍发展的重要因素。目前对于由肥胖引起认知障碍的病理机制研究多数集中在线粒体功能障碍和神经炎症等方面,这些因素均可阻碍脑胰岛素信号通路,导致认知功能损伤。改善大脑胰岛素抵抗或许是逆转由肥胖等代谢紊乱性疾病导致认知损伤的一种较为有效的治疗策略。该文根据近年来的相关研究进展,综述了由肥胖导致的氧化应激、慢性低度炎症、糖脂代谢紊乱对大脑胰岛素信号通路的影响机制,以及由于脑内胰岛素作用失调引起的突触可塑性、神经元信号传导及神经保护作用和脑内淀粉样蛋白代谢等改变,进一步导致认知障碍发生的机制。

Obesity is the main cause of insulin resistance,while insulin resistance is an important factor in the development of brain cognitive impairment.At present,most studies on the pathological mechanism of obesity-induced cognitive impairment focus on factors including mitochondrial dysfunction and neuroinflammation,etc.All these factors can block the brain insulin signaling pathway and lead to cognitive impairment.Thus improving brain insulin sensitivity may be the effective strategy to reverse cognitive impairment caused by obesity or other metabolic diseases.Based on literatures published in recent years,this review formulates and summarizes the mechanisms by which oxidative stress,chronic low-grade inflammation and glucolipid metabolic disorders resulted from obesity affect insulin action in the brain.The impairment of insulin-mediated synaptic plasticity,interference of neuronal signaling and neuroprotection,and abnormal amyloid metabolism caused by brain insulin dysfunction are also elaborated,which further lead to the occurrence of cognitive impairment.