Effect of Nutrition on Drug-Induced Liver Injury: Insights from a High-Fat Diet Mouse Model

A high-fat diet may influence susceptibility to drug-induced liver injury, though the direction and mechanism of this effect are not well characterized. This study compared acetaminophen-induced hepatotoxicity in female mice fed a normal diet versus a high-fat diet for 15 weeks prior to a single toxic acetaminophen dose, with pharmacokinetic analysis performed using Phoenix WinNonlin. Mice on the high-fat diet showed lower liver injury markers and lower plasma acetaminophen concentrations but two-fold higher drug clearance and volume of distribution compared with normal-diet mice, despite notable histopathological changes. The findings suggest a high-fat diet reduces susceptibility to acetaminophen-induced liver injury in this model, highlighting the potential need to consider nutritional status when assessing hepatotoxicity risk.