Regulating PPARG Reduces Lipid Accumulation in Microglia and Promotes Functional Recovery After Spinal Cord Injury
Spinal cord injury (SCI) substantially affects functional capacity and the immune system plays a crucial role in recovery. Examining alterations in microglia metabolism can lead to improved repair mechanisms; however, the molecular subtyping of microglia lacks consensus. In this study, the effects of SCI on macrophages and microglia in mice are investigated to identify tailored therapeutic targets and interventions for patients with SCI. Macrophages infiltrate the spinal cord shortly after injury; however, infiltration decreases over time. Microglial phagocytosis of myelin debris is associated with increased lipid accumulation. Macrophage deletion improves outcomes, whereas microglial deletion worsens them. The PLIN2+ microglia subtype in lipid droplet formation shows abnormal activation of the Pparg signaling pathway compared with that with other subtypes. PPARG promotes lipid metabolism and recovery, and atorvastatin (a PPARG agonist) reverses altered metabolic processes. Macrophages and microglia play complex roles in SCI. Targeting PPARG and its agonists is a promising therapeutic approach for SCI.
Authors
- Jin Fan
- Yongxiang Wang (ORCID: https://orcid.org/0000-0003-3763-7411)
- Mengyuan Wu (ORCID: https://orcid.org/0000-0002-1429-122X)
- Tao Jiang (ORCID: https://orcid.org/0000-0002-8529-4487)
- Yang Su (ORCID: https://orcid.org/0000-0001-5390-8192)
- Guoyong Yin (ORCID: https://orcid.org/0000-0002-7268-5374)
- Xiajia Wu (ORCID: https://orcid.org/0000-0002-8904-1321)
- Jian Chen (ORCID: https://orcid.org/0000-0003-1075-3148)
- Jiayun Liu (ORCID: https://orcid.org/0000-0003-0293-247X)
- Shujun Zhang (ORCID: https://orcid.org/0000-0002-7755-4699)
- Xiaodong Guo (ORCID: https://orcid.org/0000-0001-9429-457X)
- Qingqing Li (ORCID: https://orcid.org/0000-0002-1154-3719)
- Wei Zhou (ORCID: https://orcid.org/0000-0002-0507-2033)
- Tao Qin (ORCID: https://orcid.org/0009-0005-2364-1868)
- Shujie Zhao (ORCID: https://orcid.org/0000-0002-8658-9332)
- Baorong He (ORCID: https://orcid.org/0000-0001-5523-8006)
- Mingran Luo (ORCID: https://orcid.org/0000-0002-5346-3266)
- Peng Gao (ORCID: https://orcid.org/0009-0008-1896-5608)
Institutions
- Jiangsu Second Normal University (CN)
- Soochow University (CN)
- Xi'an Honghui Hospital (CN)
- Wuhan Union Hospital (CN)
- Wuxi Ninth People's Hospital (CN)
- Northern Jiangsu People's Hospital (CN)
- Union Hospital (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-09-12
- DOI
- https://doi.org/10.1002/advs.202506313
- Citations
- 1
- Primary Topic
- Spinal Cord Injury Research
- Type
- article
- Field-Weighted Citation Impact
- 1.47