Single-cell landscape of human adipose tissue reveals THBS1 as a potential driver of fibro-inflammation in metabolic disease.

THBS1-high fibro-inflammatory adipose stem cell and adipocyte subpopulations are enriched in human visceral adipose tissue from obesity and obesity with type 2 diabetes versus lean controls.

• Why it matters: Adipose tissue complexity is linked to metabolic disease, but the mechanisms driving adipose dysfunction and fibro-inflammation across metabolic states remain unclear.
• What they did: The study built a single-nucleus and bulk transcriptomic atlas from an ethnically homogeneous cohort, using snRNA-seq plus in vitro, ex vivo, and in vivo gain-of-function and antibody neutralization to test THBS1.
• The result: THBS1 promotes adipose fibrosis and inflammation via macrophage-mediated TGFβ activation, and THBS1 inhibition attenuates fibro-inflammatory features in metabolically dysfunctional adipose tissues.