Macrophage activation of the TREM2-DAP12-SYK pathway shapes the adipose tissue microenvironment in obesity and unveils the therapeutic potential of natural compounds egcg and SMRR
Luoying W., Xingcheng Y., Donghang C., Mengtuan L., Ping W., Lijuan Z.
Animal Study with a reported sample of 434, published in Front Immunol (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
- Front Immunol (2025)
- Reported sample size
- 434
- Source database
- Europe PMC
- PMID
- 41459526
- PMCID
- PMC12739555
- DOI
- 10.3389/fimmu.2025.1694985
- Citations
- 1
Abstract (original English)
Obesity is a major global health burden, with current therapies limited by metabolic adaptation and adverse effects. Although transcriptomic studies reveal widespread gene alterations in obesity, key drivers and their cell-specific origins in adipose tissue remain unclear. Defining these regulators is critical for understanding immune-metabolic imbalance and developing targeted interventions. We integrated bulk transcriptomics (n=434) with single-cell RNA-seq (194,608 cells from 24 adipose samples) to identify BMI-associated gene modules and macrophage regulatory programs. Cell-specific networks, subtype-specific gene regulatory networks, pseudotime trajectories, and cell-cell communication analyses delineated macrophage heterogeneity. Molecular docking assessed interactions between candidate drugs and the TREM2-DAP12-SYK pathway, and in vivo studies evaluated the therapeutic potential of EGCG and SMRR in high-fat diet mice. Our analyses revealed significant molecular and microenvironmental differences between healthy and obese adipose tissue. Eight BMI-associated genes-SYK, CD86, CSF1R, HCK, TYROBP, LAPTM5, ITGB2, and ACTB-were predominantly expressed in macrophages. Single-cell profiling identified macrophage subtypes (C4, C6, C10) with distinct regulatory roles in adipocyte communication. Dysfunction of the TREM2-DAP12-SYK axis underpinned obesity-associated macrophage state
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.
How we grade evidenceBrowse all related research
Filter the research library by this study's title keywords, author, or publication year.