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.

ABSTRACT: 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 candid

SUBMITTER: Luoying W 

PROVIDER: S-EPMC12739555 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature