Thyroid Dysfunction Induced by Fungicide Famoxadone Exposure Contributes to Nonalcoholic Fatty Liver Disease in Male Mice: In Vivo, In Vitro, and In Silico Studies.

Thyroid dysfunction has become a serious public health problem, which is considered a trigger of nonalcoholic fatty liver disease (NAFLD). Pesticide exposure could contribute to thyroid dysfunction and NAFLD, but the relationship between these factors remains unclear. In this study, the effects of subchronic famoxadone exposure on thyroid and liver at no observed adverse effect level (NOEL) related concentrations were investigated using in vivo, in vitro, and in silico models. Famoxadone caused hepatic steatosis, lipid metabolism disorder, and liver oxidative stress and induced NAFLD in male mice. The suppression of hepatic fatty acid ß-oxidation was the key factor of NAFLD, which was highly associated with hypothalamic-pituitary-thyroid (HPT) axis hormones disorder. Famoxadone disrupted thyroid hormone biosynthesis by causing thyroid follicle aberrations and abnormal HPT axis-related gene expression. In vitro studies confirmed that famoxadone inhibited the transport of thyroxine (T4) into hepatocytes and the conversion of T4 to triiodothyronine (T3). In silico studies verified that famoxadone interfered with the binding of thyroid hormones to proteins mediating thyroid hormone transport, conversion, and activation. This study comprehensively reported the association between NAFLD and thyroid dysfunction caused by famoxadone, providing new perspectives for the health risk evaluation of pesticides with a similar structure in mammals.

A microbiome abundant environment remodels the intestinal microbiota and improves resistance to obesity induced by chlorpyrifos in mice.

There is a growing consensus that the appropriate microbiome abundant environment actuates microbiota changes to influence human health. Whether living environment reacts on the threat of contaminants and the underlying mechanism remain largely unknown. Therefore, we constructed microbiome abundant environment models, focusing on their regulatory effects on the obesity induced by the exogenous chemical chlorpyrifos (CPF) and the related mechanisms. The results uncovered that the constructed farm and woodland microbiome abundant environment could protect mice against CPF-induced obesity effectively. The microbiome abundant environment regulated CPF-induced microbiota imbalance, characterized by an increase in Lactobacillus abundance. These altered microbiotas modified the intestinal immune system by increasing the expression of Foxp3 and IL-10, and mitigated intestinal barrier injury by upregulating the expression of IL-22 and intestinal tight junction proteins. Fecal microbiota transplantation could receive similar phenotypes on alleviating CPF-induced obesity development. Our results demonstrate that the microbiome abundant environment attenuates exogenous chemical-induced health risks by remodeling the intestinal microbiota, improving the intestinal ecosystem, and preventing intestinal epithelial leakage.