Von Willebrand Factor Deficiency Improves Hepatic Steatosis, Insulin Resistance, and Inflammation in Mice Fed High‐Fat Diet

OBJECTIVE: The aim of this study was to investigate the effect of Von Willebrand factor (VWF) on high-fat diet (HFD)-induced hepatic steatosis, insulin resistance, and inflammation in mice. METHODS: The expression of VWF was detected in obese mice. Wild-type and VWF knockout mice were fed a normal chow diet or an HFD, and then biomedical, histological, and metabolic analyses were conducted to identify pathologic alterations. Inflammatory cytokine levels and the number of hepatic macrophages were determined in these mice fed an HFD. RESULTS: VWF expression was significantly increased in obese mice. VWF(-/-) mice were less obese and had improved hepatic steatosis, balance of lipid metabolism, and insulin resistance in response to HFD. Furthermore, VWF deficiency attenuated HFD-induced systemic and hepatic inflammation. In addition, VWF deficiency rescued the abnormal accumulation of hepatic macrophages. CONCLUSIONS: These data demonstrated VWF deficiency improves hepatic steatosis, insulin resistance, and inflammation. Furthermore, the protective effects are mediated via regulation of hepatic macrophages.