Work

Apremilast attenuates hepatic steatosis and metabolic dysfunction in a murine model of MASLD: Implications for patients with Psoriatic disease

Year: 2025

Type: article

Abstract: BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of morbidity, linked to obesity, type 2 diabetes, and cardiovascular disease. Psoriatic disease (PsD), a chronic inflammatory condition, often coexists with MASLD, exacerbating systemic inflammation and cardiometabolic risk. Apremilast, a selective PDE4 inhibitor approved for PsD, may provide additional metabolic benefits by improving weight, lipid metabolism, and insulin sensitivity. OBJECTIVE: To evaluate the effects of apremilast on metabolic dysfunction, hepatic steatosis, and systemic inflammation in PsD patients with metabolic comorbidities, and to investigate mechanistic impact in a murine model of diet-induced MASLD. METHODS: Twenty PsD patients treated with apremilast were stratified by metabolic comorbidities. Glucose metabolism and liver function were monitored for 6 months. In parallel, C57BL/6 J mice were fed chow or GAN diet. After 14 weeks, apremilast (10 mg/kg/day) was administered for two weeks. Body weight, adiposity, liver biomarkers, insulin resistance, histology, and proteomics were evaluated. RESULTS: In PsD patients with comorbidities, apremilast reduced fasting insulin, HOMA-IR, transaminases, and the hepatic steatosis index. GAN-fed mice developed steatosis, increased fat mass, and elevated alanine aminotransferase (ALT) and HOMA-IR levels. Apremilast reduced body weight, ALT, insulin resistance, and hepatic fat. Histology confirmed a decrease in fibrosis. Proteomic profiling showed modulation of inflammatory, fibrotic, and lipid metabolic pathways, partially reversing GAN-induced proinflammatory signatures in liver, adipose tissue, and muscle. CONCLUSIONS: Apremilast ameliorates hepatic dysfunction, improves insulin sensitivity, and reduces systemic metabolic dysfunction in a murine MASLD model. These findings support its therapeutic potential in PsD patients with metabolic disease, offering both anti-inflammatory and metabolic benefits.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2025.118757