Increased hepatic expression is a major determinant of serum alanine aminotransferase elevation in mice with nonalcoholic steatohepatitis

Liver International : Official Journal of the International Association for the Study of the Liver
Rui LiuPeter F Whitington

Abstract

Serum alanine aminotransferase (ALT) is a biomarker for hepatitis of various aetiologies including fatty liver disease. Increased serum ALT is thought to be related to its increased release from dying hepatocytes. We sought to understand the mechanisms by which serum ALT is elevated in a mouse model of experimental fatty liver disease where hepatocyte death is minimal. To induce fatty liver disease, female A/J mice were fed a methionine-choline deficient (MCD) diet for up to 12 weeks. Serum and liver ALT expression and hepatic inflammation, necrosis and apoptosis were assessed and expressed relative to their expressions in control-diet-fed mice. Feeding mice the MCD diet produced hepatic steatosis with minimal hepatic inflammation or necrosis. Liver cell apoptosis was not significantly increased by MCD diet treatment. Conversely, serum ALT activity was approximately four-fold increased at 12 weeks of diet treatment, and ALT protein expressions in serum were correspondingly increased: ALT1 1.7-fold and ALT2 1.9-fold at 12 weeks. The expressions of ALT1 and ALT2 protein in liver increased over 2-12 weeks of MCD treatment. At 12 weeks, liver ALT1 protein was 2.27+/-0.31-fold increased and ALT2 protein 4.72+/-0.48-fold increased re...Continue Reading

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