Role of ADAMTS13 in diet-induced liver steatosis

Previous studies, predominantly based on increased or decreased plasma levels, have reported conflicting data on a potential functional role of ADAMTS13 in the pathogenesis of liver diseases, including non-alcoholic steatohepatitis (NASH). The aim of the current study was to evaluate whether ADAMTS13 deficiency affects development of NASH. Therefore, male wild-type (WT) and Adamts13 deficient (Adamts13(-/-)) mice were kept on a steatosis-inducing diet devoid of methionine and choline (MCD) or a control diet (MCC) for 4 weeks. Induction of NASH did not affect plasma ADAMTS13 antigen levels of WT mice. MCD as compared with MCC feeding resulted in reduced body and liver weight with no differences between the genotypes. Plasma levels of the liver enzymes AST and ALT were significantly higher for MCD vs. MCC fed Adamts13(-/-) and WT mice, however were not different between the genotypes. Liver triglyceride levels were also higher after MCD feeding, but were not different between WT and Adamts13(-/-) mice. Adamts13(-/-) mice on the two diets exhibited higher insulin sensitivity when compared with WT mice. On the MCC diet, the genotype did not show clear histological abnormalities in the liver, whereas severe steatosis and fibrosis were observed on MCD diet, however were comparable for both genotypes. This was supported by comparably enhanced hepatic expression in the two genotypes on MCD diet of the steatosis marker CD36 and of the fibrosis marker tissue inhibitor of metalloproteinase 1. Thus, the results of the current study do not support a functional role of ADAMTS13 in this murine model of NASH.