Research Progress on Anti-Inflammatory Adipokine SFRP5-Mediated Lipid Metabolism and Its Potential Role in Neural Development.

Authors

Qianfang Jia, Zihan Li, Tianyi Yang, Weihua Yang, Wei Chi

Published in

Immunity, inflammation and disease. Volume 14. Issue 6. Pages e70469.

Abstract

To systematically review the structural features of secreted frizzled‑related protein 5 (SFRP5) and its dual regulation of canonical/non‑canonical Wnt signaling, analyze its association with metabolic disorders, and specifically explore the role and mechanisms of the SFRP5-lipid metabolism axis in neural and optic nerve development.
A systematic literature search was performed to review the molecular structure of SFRP5, its regulation of Wnt pathways, and its relationship with metabolic dysregulation. The mechanisms by which SFRP5 modulates the microglia/astrocyte‑mediated neuroimmune microenvironment, myelination, synaptic plasticity, and neuronal mitochondrial energy homeostasis were analyzed, and current therapeutic strategies targeting the SFRP5 network were summarized.
SFRP5 participates in normal central nervous system development by shaping the neuroimmune microenvironment, promoting myelination, regulating synaptic plasticity, and maintaining mitochondrial energy balance. Under obese and diabetic conditions, downregulation of SFRP5 leads to overactivation of Wnt5a/JNK signaling, resulting in lipid metabolic disturbances and neuroinflammation. These changes share common pathological features with neurodevelopmental disorders such as autism spectrum disorder, intellectual disability, optic nerve hypoplasia, and retinal vascular dysplasia. The SFRP5-lipid metabolism axis plays a critical role in neural and optic nerve development, and its dysregulation underlies the neuropathology associated with metabolic diseases. Therapeutic interventions explored to date-including recombinant protein, gene therapy, small‑molecule activators, and acupuncture-have shown promising potential.
The SFRP5-lipid metabolism axis represents a key link connecting metabolic disorders with neurodevelopmental abnormalities. Future research should focus on spatiotemporal specificity at single‑cell resolution, elucidation of gene-environment interactions, and the development of efficient central nervous system delivery systems, thereby providing new avenues for the prevention and treatment of neural and optic nerve developmental abnormalities.

PMID:
42324474
Bibliographic data and abstract were imported from PubMed on 22 Jun 2026.

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