Dietary fructose regulates hepatic manganese homeostasis in female mice

Arginase, an enzyme dependent on manganese (Mn), plays a crucial role in the production of urea and processing of ammonia in the liver. Previous studies have shown that overconsumption of fructose disrupts Mn homeostasis in the liver of male mice. However, the potential sex-specific differences in the impact of fructose on hepatic Mn homeostasis remain uncertain. In this study, we provide evidence that heightened fructose intake disrupts liver Mn homeostasis in female mice. Elevated fructose exposure led to a reduction in liver Mn levels, resulting in decreased arginase and manganese superoxide dismutase (Mn-SOD) activity in the liver of female mice. The underlying mechanism involves the upregulation of carbohydrate-responsive element binding protein (ChREBP) expression and the Mn exporting gene Slc30a10 in the liver in response to fructose consumption. In summary, our findings support the involvement of fructose in liver Mn metabolism via the ChREBP/Slc30a10 pathway in female mice, and indicate that there is no disparity in the impact of fructose on hepatic Mn homeostasis between sexes.