Elevated asprosin expression exacerbates synovial inflammation by PPAR-γ-dependent mechanisms in rheumatoid arthritis.

Asprosin, a recently identified adipokine involved in metabolic and inflammatory processes. The case-control study was conducted to explore how asprosin is involved in the pathogenesis of rheumatoid arthritis (RA). 205 RA patients and 205 healthy controls were included, and MH7A cells were used for in vitro studies. Plasma asprosin was elevated in RA patients [11.4 (8.2, 15.6) ng/mL] compared to healthy controls [9.3 (7.5, 10.5) ng/mL] (Z = 5.978, P < 0.001) and exhibited moderate diagnostic accuracy (AUC = 0.67). Asprosin significantly enhanced the proliferation of synovial fibroblasts and upregulated the proinflammatory cytokines, while promoting their migratory and invasive capacities. TNF-α led to a marked downregulation of PPAR-γ, which was associated with increased asprosin levels, treatment with rosiglitazone effectively attenuated asprosin overproduction. Elevated circulating asprosin levels serve as an independent risk factor for RA and demonstrate promising diagnostic potential. PPAR-γ-mediated overexpression of asprosin contributes to synovial fibroblast dysfunction, suggesting a pathogenic role in RA development.