The role of pesticides in non-alcoholic fatty liver disease (NAFLD).

NAFLD, the most common form of liver disease worldwide, is caused by various factors including industrial chemicals and pesticides exposure. Annually, 5.2 billion pounds of pesticides are used worldwide and can contribute to liver disease, but their role is modestly studied. We hypothesize that pesticides contaminating food supply can worsen diet-induced steatosis via xenobiotic receptor activation. Two human and two rodent databases were utilized and 85% of the 330 chemicals identified associated with NAFLD were pesticides. Eight were selected for evaluating hepatic receptor activation in vitro. The majority including DDT activated hPXR/CAR and mPXR. DDT (100 mg/kg) was studied in vivo in a diet-induced obesity (DIO) model. DDT upregulated Cyp2b10 (CAR target) in control diet-fed mice. DDT decreased adiposity, but it did not affect weight gain, food consumption or insulin resistance. In conclusion, DDT improved steatosis, but it did not affect NAFLD, obesity, liver damage or diabetes caused by DIO