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J Neurotrauma. 2019 Mar 19;36(6):903-918. doi: 10.1089/neu.2018.5783. Epub 2018 Oct 30.

Activating Adiponectin Signaling with Exogenous AdipoRon Reduces Myelin Lipid Accumulation and Suppresses Macrophage Recruitment after Spinal Cord Injury.

Zhou Q1,2, Xiang H1,2, Li A3,4, Lin W1, Huang Z1, Guo J3, Wang P3, Chi Y1, Xiang K3, Xu Y1, Zhou L3, So KF3,4, Chen X1, Sun X3, Ren Y1,3,5.

Author information

1
1 Institute of Inflammation and Diseases, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
2
4 Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
3
2 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration Ministry of Education, Jinan University, Guangzhou, China.
4
5 Academician Workstation for Spinal Cord Injury, Kunming Tongren Hospital, Kunming, China.
5
3 Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida.

Abstract

Myelin-laden macrophages (mye-MΦ), resulting primarily from internalization of myelin debris by infiltrating bone marrow-derived macrophages in spinal cord injury (SCI), trigger inflammatory responses that largely contribute to secondary injury. Adiponectin, which is secreted from adipose tissue, is an important hormone that modulates macrophage inflammation. In the present study, we examined the role of adiponectin on macrophage-mediated neuroinflammation after SCI. We found that in vitro activation of adiponectin receptors (AdipoRs) by their agonist AdipoRon suppressed myelin lipid accumulation in mye-MΦ through APPL1/PPARγ/LXRα/ABCA1-mediated lipid efflux, subsequently inhibiting inflammation and restoring normal function to mye-MΦ. In vivo data further confirmed that intravenous administration of AdipoRon after SCI dampened recruitment of macrophages and reduced myelin lipid accumulation. Accordingly, AdipoRon treatment ameliorated post-SCI tissue damage and astrogliosis, resulting in improved motor function. Although there was no significant pathological exacerbation in adiponectin-null mice subjected to SCI, our work reveals a functional link between adiponectin and hematogenous macrophages in the context of SCI, suggesting that activation of adiponectin signaling is a promising therapeutic approach to mitigate mye-MΦ-mediated neuroinflammation in neurological disorders involving demyelination.

KEYWORDS:

adiponectin; chemotaxis; myelin lipid accumulation; myelin-laden macrophage; neuroinflammation; spinal cord injury

PMID:
30221582
DOI:
10.1089/neu.2018.5783

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