中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (4): 1069-1076.doi: 10.4103/NRR.NRR-D-23-01770

• 综述:退行性病与再生 • 上一篇    下一篇

肝-脑轴代谢功能障碍和炎症在肥胖诱导的神经退行性变动物模型中的作用

  

  • 出版日期:2025-04-15 发布日期:2024-06-30

Role of metabolic dysfunction and inflammation along the liver–brain axis in animal models with obesity-induced neurodegeneration

Evridiki Asimakidou1 , Eka Norfaishanty Saipuljumri2, 3, Chih Hung Lo3 , Jialiu Zeng3, *   

  1. 1 Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 2 School of Applied Science, Republic Polytechnic, Singapore, Singapore; 3 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
  • Online:2025-04-15 Published:2024-06-30
  • Contact: Jialiu Zeng, PhD, jialiu.zeng@ntu.edu.sg.
  • Supported by:
    This work was supported by a Presidential Postdoctoral Fellowship (021229-00001) from Nanyang Technological University, Singapore (to JZ); a Lee Kong Chian School of Medicine Dean’s Postdoctoral Fellowship (021207-00001) from NTU Singapore and a Mistletoe Research Fellowship (022522-00001) from the Momental Foundation, USA (to CHL).

摘要: https://orcid.org/0000-0001-7802-1432 (Jialiu Zeng)

Abstract: The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Obesity-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this relationship. Peripheral lipid accumulation, particularly in the liver, initiates a cascade of inflammatory processes that extend to the brain, influencing critical metabolic regulatory regions. Ceramide and palmitate, key lipid components, along with lipid transporters lipocalin-2 and apolipoprotein E, contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting gliosis. Peripheral insulin resistance further exacerbates brain insulin resistance and neuroinflammation. Preclinical interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal models. However, translating these findings to clinical practice requires further investigation into human subjects. In conclusion, metabolic dysfunction, peripheral inflammation, and insulin resistance are integral to neuroinflammation and neurodegeneration. Understanding these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.

Key words: Alzheimer’s disease, inflammatory cytokines, insulin resistance, lipid accumulation, metabolic dysfunction, neuroinflammation, Parkinson’s disease