Fibrosis in adipose tissue (AT)—driven by excessive deposition of extracellular matrix (ECM)—is a hallmark of AT dysfunction and obesity-related insulin resistance. Growing data point to adipogenic stem and precursor cells (ASPCs) as a pivotal source of ECM proteins and as potential instigators of AT fibrosis. In this study, we used single-cell RNA sequencing to uncover a distinct ASPC subpopulation with a strong association to ECM-related functions.
Within this particular ASPC subset, Fibulin-7 (FBLN7), a secreted glycoprotein, showed a pronounced increase in obese mice. In humans, FBLN7 levels rose in visceral fat of obese individuals and correlated with various clinical metabolic traits. Functional experiments indicated that, under caloric excess, ASPCs lacking FBLN7 exhibited reduced AT fibrosis and inflammation, accompanied by improved systemic metabolic health. Conversely, removing FBLN7 in ASPCs dampened TGF-β–induced fibrogenic responses, while overexpression of FBLN7 amplified these responses.
Mechanistically, FBLN7 binds to thrombospondin-1 (TSP1) through its EGF-like calcium-binding domain, stabilizing the TSP1 protein. This stabilization promotes activation of latent TGF-β, which then engages the TGFBR1/Smad signaling axis to drive fibrosis. Importantly, the researchers developed an anti-FBLN7 neutralizing antibody that markedly reduced diet-induced AT fibrosis, highlighting FBLN7 as a major ASPC-derived regulator of AT fibrosis and a promising therapeutic target.
Source:
Yu, H., et al. (2025). Fibulin-7 in progenitor cells promotes adipose tissue fibrosis and disrupts metabolic homeostasis in obesity. Protein & Cell. DOI: 10.1093/procel/pwaf084.
