摘要
高脂饮食模式严重危害人类健康,过量摄入的饱和脂肪酸可穿透血脑屏障,在中枢神经系统中诱发一种可引起机体代谢功能障碍的非典型性炎症反应。下丘脑是调节能量动态平衡的关键区域,其炎症反应是多种代谢性疾病的共同致病基础。下丘脑中慢性低度炎症会表现为神经胶质细胞的增生、炎性细胞因子的激活及内质网应激、氧化应激和自噬缺陷等胞内应激的增强。高脂饮食通过活化传统炎症信号通路,诱导下丘脑胰岛素及瘦素抵抗,影响下丘脑中促食神经元和厌食神经元形成的食欲调节网络的平衡,最终导致食物摄入量和体重增加。二甲双胍(metformin,MF)是一种具有广泛靶点的降糖药物。在中枢神经炎症发展进程中,MF可抑制下丘脑神经胶质细胞的增生、调节神经胶质细胞释放的促炎因子和抗炎因子之间的平衡;通过发挥抗炎和抗氧化作用,干预高脂饮食所致的下丘脑胞内应激;通过调节下丘脑中PI3K-Akt、STAT3、AMPK和mTOR等信号通路,影响胰岛素和瘦素信号通路,下丘脑瘦素和胰岛素信号传导的改善,促使食欲调节神经元的表达平衡向厌食因子转移,使机体的食物摄入量降低和能量消耗增加,从而减少下丘脑炎症介导的肥胖的发生。本文对高脂饮食诱导的下丘脑炎症、MF改善下丘脑炎症的分子机制作一综述,以期为MF的相关应用研究提供理论参考。
High-fat diet is a serious risk to human health.Excessive intake of saturated fatty acids can penetrate the blood-brain barrier and induce atypical inflammatory response in the central nervous system,which can cause metabolic dysfunction in the body.The hypothalamus is a key region that regulates the dynamic balance of energy,and its inflammatory response is the common pathogenic basis for many metabolic diseases.Chronic low-grade inflammation in the hypothalamus can be manifested by proliferation of glial cells,activation of inflammatory cytokines and enhanced intracellular stresses such as endoplasmic reticulum stress,oxidative stress and defective autophagy.High-fat diet induces hypothalamic insulin and leptin resistance through activation of the traditional inflammatory signaling pathway.Insulin and leptin resistance affects the balance of appetite regulation networks formed by feeding-promoting and feeding-suppressing neurons in the hypothalamus,ultimately leading to excessive food intake and weight gain.Metformin(MF)is a glucose-lowering drug with a wide range of targets.MF can inhibit the proliferation of hypothalamic glial cells and regulate the balance between pro-and anti-inflammatory factors released by glial cells during the development of central neuroinflammation.MF exerts anti-inflammatory and antioxidant effects to regulate hypothalamic intracellular stress caused by high-fat diet,and modulates such as PI3K-Akt,STAT3,AMPK and mTOR pathways to influence insulin and leptin signaling in the hypothalamus.The improved hypothalamic leptin and insulin signaling shifts the balance of appetite regulatory neuron expression towards anorexia factors,resulting in decreased food intake and increased energy expenditure,reducing the incidence of hypothalamic inflammation-mediated obesity.To provide a theoretical foundation for the investigation of relevant MF applications,we discuss the hypothalamic inflammation caused by a high-fat diet as well as the molecular mechanism of MF controlling hypothalamic inflammation in this paper.
作者
崔思瑶
周璐瑾
常晓彤
CUI Si-Yao;ZHOU Lu-Jin;CHANG Xiao-Tong(Key Laboratory of Clinical Diagnostic,Hebei North University,Zhangjiakou 075000,Hebei,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2023年第10期1427-1435,共9页
Chinese Journal of Biochemistry and Molecular Biology
基金
河北省高等学校科学技术研究项目(No.ZD2018076)
河北北方学院自然科学项目(No.YB2020012)资助。
