Novel Cell-to-Cell Communications Between Macrophages and Fibroblasts Regulate Obesity-Induced Adipose Tissue Fibrosis.

Summary

Using single-cell and spatial transcriptomics in diet-induced obese mice, the authors identify a Mincle+ macrophage subcluster in crown-like structures that induces oncostatin M to suppress collagen gene expression in nearby fibroblasts. Loss of Osm in immune cells exacerbated adipose fibrosis in vivo, and human adipose tissue showed correlated MINCLE–OSM expression. This defines an immunometabolic axis that restrains fibrosis during obesity.

Key Findings

• Identified a Mincle-expressing macrophage subcluster localized to crown-like structures in obese adipose tissue.
• Mincle signaling upregulated oncostatin M, which suppressed collagen gene expression in adipose fibroblasts.
• Immune-cell Osm deficiency increased adipose tissue fibrosis in vivo; human obese adipose showed positive MINCLE–OSM correlation.

Clinical Implications

Targeting the Mincle–OSM pathway could be explored to limit adipose tissue fibrosis and metabolic complications in obesity. Biomarkers such as MINCLE/OSM expression in adipose biopsies may stratify fibrotic risk.

Limitations

• Primary mechanistic work in mouse models; human causality not established.
• Therapeutic manipulability and safety of targeting Mincle–OSM require evaluation.

Future Directions

Test pharmacologic or biologic modulation of Mincle–OSM in preclinical models; define clinical biomarkers and assess associations with metabolic outcomes in humans.