The Impact of a Short-term High-fat Diet on Coagulation Function in a Mouse Model and Its Role in Exacerbating Concanavalin A-Induced Liver Injury

Background Recently, the number of patients with non-alcoholic fatty liver disease (NAFLD) and its more advanced condition, non-alcoholic steatohepatitis (NASH), has been increasing. These patients are at a higher risk of cardiovascular events and thromboembolism. However, the direct impact of high-fat diet (HFD), a cause of NAFLD, on liver coagulation function is not well understood. Previously, we demonstrated that a short-term, 4-day intake of a HFD exacerbates concanavalin A (Con A)-induced acute liver injury in mice by promoting coagulation and inflammation. This model demonstrates that the liver exposed to a short-term HFD is vulnerable even before disease onset. In this study, using this model, we elucidated the detailed mechanisms by which short-term HFD intake promotes coagulation, considering primary and secondary hemostasis. Methods C57BL/6 mice normally fed a normal diet (ND) were subjected to a HFD for 4 days. Liver tissue and blood samples were collected before and 4 and 24 hours after Con A administration. Histological analysis, flow cytometry for platelet analysis, and blood coagulation tests related to secondary hemostasis were performed. Results Even with short-term consumption of a HFD alone, platelet and fibrinogen levels increased in the peripheral blood and liver. Additionally, when Con A was administered to mice on a short-term HFD, an increase in P-selectin expression was observed in the liver, with no upregulation in peripheral blood platelets. Furthermore, in mice subjected to a short-term HFD and treated with Con A, prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed. Conclusions Consuming a HFD in short-term can enhance primary and secondary hemostasis, thereby increasing the risk of thrombosis. These conditions are presumed to be a risk factor that exacerbates Con A-induced liver injury. The findings provide insight into early intervention strategies for chronic liver diseases, such as NAFLD and NASH.