Researchers have identified a key role for the protein Fibulin-7 (FBLN7) in the development of fibrosis in adipose tissue, a process linked to obesity-related insulin resistance and metabolic dysfunction. Using single-cell RNA sequencing, scientists found a distinct group of adipogenic stem and precursor cells (ASPCs) that are closely involved with extracellular matrix (ECM) function.
The study showed that FBLN7 expression was notably higher in obese mice. In humans, increased levels of FBLN7 were also observed in visceral fat among obese individuals, with these levels correlating to clinical metabolic traits. Functional experiments demonstrated that mice lacking FBLN7 specifically in ASPCs experienced less adipose tissue fibrosis and inflammation after consuming excess calories, along with improvements in overall metabolic health.
Further investigation revealed that removing FBLN7 from ASPCs reduced fibrogenic responses triggered by TGF-β, while overexpressing FBLN7 intensified these responses. The researchers discovered that FBLN7 interacts with thrombospondin-1 (TSP1), stabilizing the TSP1 protein and promoting the activation of latent TGF-β into its active form. This process enhances signaling through the TGFBR1/Smad pathway.
Additionally, the team developed an anti-FBLN7 neutralizing antibody that significantly reduced diet-induced adipose tissue fibrosis in experimental models. According to the authors, "These results suggest that FBLN7, produced by ASPCs, exerts a major influence in the development of AT fibrosis and may represent a potential target for therapeutic intervention."
