Cadmium exposure during adolescence and young adulthood induces signatures of metabolic dysfunction-associated steatotic liver disease.

Due to its pervasiveness in the environment, its long biological half-life in tissues, and its association with adverse health effects in nearly all organ systems, the heavy metal cadmium (Cd) has been designated a top ten chemical of major public health concern by the World Health Organization. We have demonstrated that exposure to Cd during perinatal development programs metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver disease in the world. Adolescence presents another critical window of susceptibility to environmental stressors; however, the impacts of Cd exposure during this period on the health of the liver are not known. To help bridge this knowledge gap, we exposed juvenile C57BL/6 J mice to Cd via their drinking water for 14 weeks. We performed histological, biochemical, and molecular analyses on liver tissue to determine if exposure to Cd during adolescence and young adulthood also induces MASLD. We found that Cd exposure altered hepatic lipid homeostasis via the perturbation of steatosis gene expression and lipid species abundances. Additionally, Cd exposure triggered a hepatic antioxidant response and activated an imprinted gene network (IGN) which we have previously implicated in MASLD. Our results show that adolescence, albeit to a lesser degree than the perinatal period, is a critical window of susceptibility to Cd-induced changes in hepatic metabolic homeostasis.