Bile Acid Alterations Characterize the Early Onset and Progression of Nonalcoholic Fatty Liver Disease in Young Mice Fed with High Fat and Fructose Diet

Scope Bile acids (BAs) are closely associated with obesity and non‐alcoholic fatty liver disease (NAFLD). How BAs change within the enterohepatic circulation during the onset and progression of NAFLD as biomarkers deserves to be explored. Methods and Results Four‐week‐old young mice were fed with high‐fat diet plus 4% v/w fructose drinking water (HFF) or normal diet with tap water (ND) for 4 and 12 weeks. In comparison, eight‐week‐old adult mice were fed with HFF or ND for 12 weeks. BAs were measured in six different anatomical sites to evaluate the systematic changes of BAs within the enterohepatic circulation. The dysregulated BA metabolism had occurred in HFF after 4‐week intervention, represented by increased primary BAs and decreased hyocholic acid (HCA) species. After 12 weeks, the impact was more significant with increased secondary BA synthesis and excretion, particularly for lithocholic acid (LCA) species. More interestingly, the BA changes were more significant in younger mice in response to 12‐week diet intervention. Conclusions The enterohepatic circulation of BAs changed with the development of NAFLD, and the younger mice were more susceptible to the unhealthy diet. HCA and LCA species may be potential biomarkers for predicting the development of NAFLD.