Evidence map›Paper›PMID 41517974›Full record

ArticleCNS neuroscience & therapeutics2026

PGC-1α Transcriptionally Regulated by ChREBP Mitigates Neuropathic Pain Through Promoting Microglial Fatty Acid Oxidation and Anti-Inflammatory Response.

Ziwei Hu, Jiahui Pang, Xinli Liu, Yun Zhao, Yi Lu, Hui Chen, Hui Zeng, Youxin Yu, Yubai Zhao, Lijie Gao and 6 more

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
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  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Ziwei HuCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Jiahui PangCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Xinli LiuCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Yun ZhaoCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Yi LuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Thoracic Surgery and Oncology, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Hui ChenCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Hui ZengCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Youxin YuCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Yubai ZhaoDepartment of Clinical and Rehabilitation Medicine, Guiyang Healthcare Vocational University, Guizhou, China.
Lijie GaoCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.ORCID 0000-0002-2361-8159
Xuefei ZhangCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Jian JinCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Kangling WangCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.ORCID 0000-0003-4335-7811
Yu ShiCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.ORCID 0000-0001-8225-8678
Hongrui ZhanDepartment of Rehabilitation, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
Wen WuCenter of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.ORCID 0000-0002-5576-2999

Funding

Guangdong Basic and Applied Basic Research Foundation 2021A1515010135Guangdong Basic and Applied Basic Research Foundation 2023A1515010200Guangzhou Municipal Science and Technology Project 10.13039/501100010256the National Natural Science Foundation of China 82172526the National Natural Science Foundation of China 82372553the National Natural Science Foundation of China 82402954
6 · The paper itself

Abstract

backgroundNeuropathic pain (NP), a chronic disorder caused by somatosensory nervous system lesions, severely impairs the quality of life. Microglial metabolic reprogramming and neuroinflammation drive NP progression. Although ChREBP (key metabolic regulator) protects against NP, its specific mechanisms remain unclear.

methodsNP rat model was established via spared nerve injury (SNI) surgery, and mechanical allodynia was evaluated using Von Frey tests. ChREBP expression in microglia was detected through immunofluorescence, RT-qPCR, and western blot. Functional studies involved ChREBP knockdown/overexpression to assess effects on microglial polarization, neuroinflammation, neuronal excitability, pain behaviors, and fatty acid metabolism. Mechanisms were explored via dual-luciferase reporter and chromatin immunoprecipitation assays.

resultsMechanical pain thresholds were significantly decreased on the ipsilateral side after SNI. ChREBP was upregulated in SDH microglia after SNI and in LPS-stimulated microglia in vitro. ChREBP knockdown inhibited anti-inflammatory microglial polarization, exacerbated neuroinflammation, and aggravated pain. Conversely, ChREBP overexpression promoted the anti-inflammatory phenotype, suppressed neuroinflammation, and alleviated pain. ChREBP enhanced microglial fatty acid oxidation and energy metabolism. Mechanistically, ChREBP bound to the TFBS1 site on the PGC-1α promoter to activate its transcription. PGC-1α overexpression rescued the impairments caused by ChREBP knockdown, including reduced fatty acid oxidation, suppressed anti-inflammatory polarization, elevated inflammatory factors, and increased neuronal excitability. The protective effects of ChREBP were attenuated by the fatty acid oxidation inhibitor Etomoxir.

conclusionsChREBP alleviates NP by enhancing microglial fatty acid oxidation and anti-inflammatory phenotype via PGC-1α transcriptional activation, revealing a novel metabolic-immune axis for potential NP therapy.

Indexed as

Fatty AcidsMicrogliaNeuralgiaPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaAnimalsMaleNeuroinflammatory DiseasesOxidation-ReductionRatsRats, Sprague-DawleyFatty AcidsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, ratChREBPfatty acid oxidationmicroglianeuropathic painPGC‐1α

Identifiers

PMID41517974
PMCPMC12789879

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.