Neuroplastin-55 is a receptor of Manf and protects against diet-induced obesity by promoting adipose browning
Jia Q., Zhang J., Song H., Chen J., Zhang Z., Yu H.
Animal Study, published in Proc Natl Acad Sci U S A (2025) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Proc Natl Acad Sci U S A (2025)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 41284862
- PMCID
- PMC12685124
- DOI
- 10.1073/pnas.2515526122
- Citations
- 1
Abstract (original English)
The browning of white adipose tissue (WAT) enhances thermogenesis and holds great potential in obesity treatment. Membrane receptors have been proven as essential factors during WAT browning. In this study, we found that transmembrane receptor neuroplastin-55 (Np55) was markedly upregulated in the adipose tissue of both obese individuals and mice. Fat-specific Np55 knockout (Np55 FKO ) sensitized mice to high-fat diet-induced obesity and metabolic disorders, which was attributed to impaired energy expenditure and WAT browning. We identified that mesencephalic astrocyte-derived neurotrophic factor (Manf) acts as a ligand for Np55 with high binding affinity. Mechanistically, Np55 forms a complex with tumor necrosis factor receptor associated factor-2 (TRAF2) and apoptosis signal-regulating kinase 1 (ASK1) to activate p38 mitogen-activated protein kinase (MAPK) signaling pathway and conduct WAT browning after Manf stimulation. Additionally, we identified a single-nucleotide polymorphism (rs2470738600) in Manf compromised the binding affinity to Np55 and thermogenic capacity. Finally, we showed that Np55 is indispensable for Manf-induced thermogenesis and weight loss in obese mice. Our results underscore the pivotal role of Np55 as a receptor of Manf in maintaining metabolic homeostasis, highlighting its potential as a therapeutic target for obesity and related disorders.
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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