Liver-humanized mice: A translational strategy to study metabolic disorders

The liver is the metabolic core of the whole body. Tools commonly used to study the human liver metabolism include hepatocyte cell lines, primary human hepatocytes, and pluripotent stem cells-derived hepatocytes in vitro, and liver genetically humanized mouse model in vivo. However, none of these systems can mimic the human liver in physiological and pathological states satisfactorily. Liver-humanized mice, which are established by reconstituting mouse liver with human hepatocytes, have emerged as an attractive animal model to study drug metabolism and evaluate the therapeutic effect in "human liver" in vivo because the humanized livers greatly replicate enzymatic features of human hepatocytes. The application of liver-humanized mice in studying metabolic disorders is relatively less common due to the largely uncertain replication of metabolic profiles compared to humans. Here, we summarize the metabolic characteristics and current application of liver-humanized mouse models in metabolic disorders that have been reported in the literature, trying to evaluate the pros and cons of using liver-humanized mice as novel mouse models to study metabolic disorders.