Single-cell landscape of human adipose tissue reveals THBS1 as a potential driver of fibro-inflammation in metabolic disease
Abstract
The cellular complexity of adipose tissue plays a critical role in the pathogenesis of metabolic disease; however, mechanisms underlying adipose dysfunction remain poorly understood. Here, we constructed a single-nucleus and bulk transcriptomic atlas of human visceral adipose tissues from an ethnically homogeneous cohort with defined metabolic states: lean with normal glucose tolerance, obesity, and obesity with type 2 diabetes. Single-nucleus RNA sequencing (snRNA-seq) revealed a fibro-inflammatory subpopulation of adipose stem cells and adipocytes characterized by high THBS1 expression, which were enriched in individuals with obesity and obesity with type 2 diabetes compared to lean controls. Through complementary in vitro (human primary ASCs, THP-1 macrophages, and Matrigel-captured mature adipocytes), ex vivo (mouse and human visceral adipose tissue explants), and in vivo (gain-of-function and antibody-mediated neutralization) experiments, we demonstrated that THBS1 promoted adipose fibrosis and inflammation via macrophage-mediated TGFβ activation, impairing adipogenesis and adipocyte function. Inhibition of THBS1 attenuated fibro-inflammatory features in metabolically dysfunctional adipose tissues. Moreover, THBS1 levels in plasma and adipocytes correlated with metabolic traits, including BMI and HbA1c. Collectively, our study provides a cellular atlas of human visceral adipose tissues across metabolic disease states and identifies THBS1 as a key pathogenic driver and potential therapeutic target.
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BibTeX
@article{jung2026singlecell,
title = {{Single-cell landscape of human adipose tissue reveals THBS1 as a potential driver of fibro-inflammation in metabolic disease}},
author = {Jisu Jung and Eun Seo Park and Na Keum Lee and Jung-Jae Lee and Uijin Juang and Qingzhi Huang and Young Suk Park and Hyung Joon Kim and Jung-Kwon Kim and Tae Jung Oh and Jae Myoung Suh and Jae Bum Kim and Joon Ho Moon and Jong Kyoung Kim and Sung Hee Choi},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-77107-w},
url = {https://www.nature.com/articles/s41467-026-77107-w},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Single-cell landscape of human adipose tissue reveals THBS1 as a potential driver of fibro-inflammation in metabolic disease
AU - Jisu Jung
AU - Eun Seo Park
AU - Na Keum Lee
AU - Jung-Jae Lee
AU - Uijin Juang
AU - Qingzhi Huang
AU - Young Suk Park
AU - Hyung Joon Kim
AU - Jung-Kwon Kim
AU - Tae Jung Oh
AU - Jae Myoung Suh
AU - Jae Bum Kim
AU - Joon Ho Moon
AU - Jong Kyoung Kim
AU - Sung Hee Choi
PY - 2026
DA - 2026/10/27
JO - Nature Communications
DO - 10.1038/s41467-026-77107-w
UR - https://www.nature.com/articles/s41467-026-77107-w
AB - The cellular complexity of adipose tissue plays a critical role in the pathogenesis of metabolic disease; however, mechanisms underlying adipose dysfunction remain poorly understood. Here, we constructed a single-nucleus and bulk transcriptomic atlas of human visceral adipose tissues from an ethnically homogeneous cohort with defined metabolic states: lean with normal glucose tolerance, obesity, and obesity with type 2 diabetes. Single-nucleus RNA sequencing (snRNA-seq) revealed a fibro-inflammatory subpopulation of adipose stem cells and adipocytes characterized by high THBS1 expression, which were enriched in individuals with obesity and obesity with type 2 diabetes compared to lean controls. Through complementary in vitro (human primary ASCs, THP-1 macrophages, and Matrigel-captured mature adipocytes), ex vivo (mouse and human visceral adipose tissue explants), and in vivo (gain-of-function and antibody-mediated neutralization) experiments, we demonstrated that THBS1 promoted adipose fibrosis and inflammation via macrophage-mediated TGFβ activation, impairing adipogenesis and adipocyte function. Inhibition of THBS1 attenuated fibro-inflammatory features in metabolically dysfunctional adipose tissues. Moreover, THBS1 levels in plasma and adipocytes correlated with metabolic traits, including BMI and HbA1c. Collectively, our study provides a cellular atlas of human visceral adipose tissues across metabolic disease states and identifies THBS1 as a key pathogenic driver and potential therapeutic target.
SN - 2041-1723
ER -