Related Experiment Video
Updated: Feb 20, 2026
Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
Role of ADAMTS13 in diet-induced liver steatosis
Lotte Geys1, Elien Roose2, Karen Vanhoorelbeke2
1Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, B‑3000 Leuven, Belgium.
Abstract:
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.
Insights
ADAMTS13 deficiency did not impact non-alcoholic steatohepatitis (NASH) development in mice. Severe steatosis and fibrosis occurred similarly in wild-type and ADAMTS13-deficient mice on a NASH-inducing diet.
Area of Science:
- Hepatology
- Biochemistry
- Genetics
Background:
- Conflicting data exists on ADAMTS13's role in liver disease pathogenesis.
- Previous studies focused on plasma levels, necessitating in vivo functional evaluation.
- Non-alcoholic steatohepatitis (NASH) is a growing concern with complex mechanisms.
Purpose of the Study:
- To investigate the functional role of ADAMTS13 in the development of non-alcoholic steatohepatitis (NASH).
- To determine if ADAMTS13 deficiency influences NASH progression in a murine model.
Main Methods:
- Male wild-type (WT) and Adamts13 deficient (Adamts13-/-) mice were fed a methionine-choline deficient (MCD) diet or a control (MCC) diet for 4 weeks.
- Evaluated body and liver weights, plasma liver enzymes (AST, ALT), liver triglyceride levels, and insulin sensitivity.
- Assessed liver histology for steatosis and fibrosis, and quantified hepatic expression of CD36 and tissue inhibitor of metalloproteinase 1.
Main Results:
- NASH induction (MCD diet) reduced body and liver weights similarly in both genotypes.
- Plasma AST and ALT levels were elevated in MCD-fed mice but comparable between WT and Adamts13-/- groups.
- Severe steatosis and fibrosis were observed in MCD-fed mice, with no significant differences between genotypes. Hepatic CD36 and TIMP1 expression were also comparable.
- Adamts13-/- mice showed higher insulin sensitivity on both diets compared to WT mice.
Conclusions:
- ADAMTS13 deficiency does not appear to play a functional role in the development or progression of NASH in this specific murine model.
- The study highlights that while NASH induces significant liver pathology, ADAMTS13 is not a key determinant in this model.
- Further research may be needed to explore other potential roles or models for ADAMTS13 in liver disease.
