Psoriasis is a chronic immune-mediated inflammatory disease with systemic manifestations beyond the skin, yet the role of subcutaneous adipose tissue (SAT) in disease biology and therapeutic response remains poorly understood. Here, we investigated inflammatory features of SAT in psoriasis and the effects of dimethyl fumarate (DMF) on this compartment. Six adults with moderate-to-severe plaque psoriasis received oral DMF for 24 weeks and were clinically evaluated measuring the Psoriasis Area and Severity Index (PASI), showing a consistent reduction in disease severity during treatment. Publicly available spatial transcriptomic data were analysed to profile inflammatory signatures in SAT clusters of psoriatic versus healthy skin. Bulk RNA sequencing was performed on SAT biopsies obtained from psoriatic plaques before and after DMF treatment in four patients. Complementary in vitro models using murine 3T3-L1 adipocytes and human adipocytes differentiated from mesenchymal stem cells were exposed to pro-inflammatory cytokines or macrophage-conditioned media (CM) with or without DMF to assess effects on inflammatory gene expression and NF-κB signalling. Spatial transcriptomics identified enrichment of inflammation-related pathways in SAT beneath psoriatic lesions. DMF treatment was associated with reduced expression of inflammatory mediators and with a shift in SAT transcriptional profile toward patterns observed in healthy tissue. In vitro, DMF significantly attenuated cytokine- and CM-induced adipocyte activation and reduced NF-κB phosphorylation in both murine and human adipocyte models. These data provide integrated clinical and experimental evidence that DMF treatment is associated with reduced disease activity and attenuation of inflammatory signalling within psoriatic SAT, supporting adipose tissue as a potentially modifiable inflammatory compartment in psoriasis.
