Platelet-activating cytokines potentially associated with MASLD-induced liver injury significantly decreased following CPAP therapy: A translational study using a fatty liver mouse model

Abstract

Background and aim

Patients with obstructive sleep apnea (OSA) and metabolic dysfunction associated steatotic liver disease (MASLD) frequently overlap due to the high prevalence of obesity. This translational study aimed to identify cytokines linking these conditions, beginning with an analysis of fatty liver in mice. Serum cytokine levels upregulated in the fatty liver mice were subsequently examined in human OSA serum samples.

Methods

Mice were fed a high-fat diet to induce fatty liver. Liver proteins were analyzed using cytokine arrays. Serum samples from seventy (70) OSA patients (with 20 non-MASLD and 50 MASLD, pre- and 6-month post-continuous positive airway pressure [CPAP] therapy) were analyzed for the cytokines identified in the mouse experiment using enzyme-linked immunosorbent assays.

Results

Four platelet-activation chemokines/cytokines (CCL5/RANTES, P-selectin, CXCL4/PF4, and CXCL5/LIX) were upregulated in mice with fatty liver. While serum levels of these factors were not significantly higher in MASLD-OSA compared to non-MASLD-OSA patients, their levels significantly decreased 6 months after the initiation of CPAP therapy, along with a reduction in mean platelet volume. CPAP compliance was significantly associated with a reduction in CCL5 levels. Additionally, a decrease in ALT levels following 6 months of CPAP therapy was significantly associated with CPAP compliance in MASLD-OSA patients.

Conclusions

While platelet-activation cytokines were not directly implicated in liver injury in MASLD-OSA patients, they decreased with CPAP therapy. CPAP compliance may play a key role in ALT reduction in MASLD-OSA patients independently of body weight changes. CCL5/RANTES may be indirectly associated with liver injury in MASLD-OSA, potentially induced through intermittent hypoxia.