Novel cell-to-cell communications between macrophages and fibroblasts regulate obesity-induced adipose tissue fibrosis [bulk RNA-seq]

Mincle (Macrophage inducible C-type lectin, clec4e) is a pattern recognition receptor expressed in innate immune cells and can sense cell death, suggesting a role in sterile inflammation. We previously showed that expression of Mincle is induced in adipose tissue macrophages during the development of obesity. Mincle accelerates adipose tissue inflammation and fibrosis, thereby exacerbating ectopic lipid accumulation and insulin resistance in the liver. In this study, we performed single-cell RNA sequencing analysis of the SVF in visceral adipose tissue from diet-induced obese mice to analyze the cell-cell interaction between Mincle-expressing macrophages and activated fibroblasts. We found that Oncostatin M (Osm), a member of the interleukin-6 cytokine superfamily secreted from Mincle-expressing macrophages, acts on fibroblasts to inhibit collagen expression. Overall design: Adipose tissue–derived fibroblasts were prepared from the SVF of HFD-fed mice using a magnetic cell sorting system (AutoMACS; Miltenyi Biotec) as CD45-, CD31-, and Ter119-negative cells. Adipose tissue–derived fibroblasts were treated with recombinant human transforming growth factor-ß1 (TGFß1) (3 ng/mL; BioLegend) or recombinant mouse Osm (3 ng/mL; BioLegend) for 24 h.