Hepatic STAMP2 alleviates polychlorinated biphenyl-induced steatosis and hepatic iron overload in NAFLD models.

Polychlorinated biphenyls (PCBs) have been associated with neurotoxicity, hepatoxicity, oncogenicity, and endocrine-disrupting effects. Although the recent studies have demonstrated that PCB exposure leads to nonalcoholic fatty liver disease (NAFLD), the underlying mechanism has remained unsolved. In this study, we examined the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, and PCB 126 in C57BL/6 mice. Male C57Bl/6 mice were fed a standard diet or a 60% high-fat diet and exposed to Aroclor 1260 (10 mg/kg or 20 mg/kg) or PCB 126 (1 mg/kg or 5 mg/kg) by intraperitoneal injection for a total of four injections (2, 3, 4, and 5 weeks) for 6 weeks. In mice, both Aroclor 1260 and PCB 126-induced liver damage, hepatic steatosis and inflammation. We also observed that PCB exposure-induced hepatic iron overload (HIO). We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable therapeutic target for NAFLD patients. Thus, we further examined whether hepatic STAMP2 is involved in PCB-induced NAFLD. We observed that hepatic STAMP2 was significantly decreased in PCB-induced NAFLD models in vivo and in vitro. Furthermore, overexpression of hepatic STAMP2 using an adenoviral delivery system resulted in improvement of PCB-induced steatosis and HIO in vivo and in vitro. Our findings indicate that enhancing hepatic STAMP2 expression represents a potential therapeutic avenue for the treatment of PCB exposure-induced NAFLD.