Prophylactic Soraphen A Treatment Attenuates Western Diet-Exacerbated IMQ-Induced Psoriasiform Inflammation

Psoriasis is a T-cell-mediated inflammatory disease amplified by metabolic stress. Acetyl-CoA carboxylase 1 (ACC1)-dependent fatty acid synthesis is required for IL-17-producing T cells. Here, we asked whether short-term systemic administration of soraphen A (SorA), a dual ACC1/2 inhibitor, modulates imiquimod (IMQ)-induced psoriasiform inflammation under normal diet (ND) and Western diet (WD) conditions. Female C57BL/6J mice were fed ND or WD for 12 weeks prior to daily intraperitoneal injections of SorA or vehicle for 10 days, followed by 5 days of topical IMQ to induce psoriasiform dermatitis. Disease severity was assessed by macroscopic, histological, transcriptional, and flow cytometric readouts. Prophylactic SorA administration had no measurable effect in ND-fed mice. In WD-fed mice, prophylactic SorA reduced erythema, back skin thickening, and epidermal hyperplasia, whereas scaling remained unchanged. Selected histological skin readouts were numerically lower, whereas the qPCR panel showed no statistically significant differences. In skin-draining lymph nodes, IL-17A⁺ CD4⁺ and CD8⁺ T-cell frequencies and numbers were significantly reduced, whereas γδT17 cells did not differ significantly. Hepatic steatosis scores were unchanged, but hepatic neutrophil infiltration was reduced. Under the present prophylactic regimen, systemic SorA administration was associated with modest attenuation of WD-exacerbated IMQ-induced psoriasiform inflammation. These findings support further preclinical evaluation of ACC-targeted immunometabolic interventions in metabolically aggravated psoriasiform inflammation.