Mechanisms of metabolic-associated fatty liver disease induced by 48-week PCB138 exposure and theabrownin intervention

作者：Jian-Rong Han, Changqian Liu, Zhiyuan Chen, Fengkai Ruan, Fanzheng Xue, Lingxiao Ye, Yi Yu, Zhenghong Zuo, Chengyong He · 发表于：Environment International · 年份：2025 · DOI：10.1016/j.envint.2025.109780 · 被引用次数：7 · 研究领域：Liver Disease Diagnosis and Treatment、Diet and metabolism studies、Diet, Metabolism, and Disease

Metabolic-associated fatty liver disease (MAFLD), linked to lipid dysregulation, poses global health risks. 2,2',3,4,4',5'-hexachlorobiphenyl (PCB138) is a persistent organic pollutant that poses potential threats to liver health due to its environmental persistence and bioaccumulation. Theabrown (TB), a natural compound extracted from black tea, exhibits lipid-lowering and antioxidant properties, but its protective effects on PCB138-induced liver injury have not been thoroughly investigated. Following a biphasic experimental design, juvenile male C57BL/6J mice were subjected to chronic PCB138 exposure (100 μg/kg, oral gavage every other day) for 48 weeks, with subsequent administration of TB (225 mg/kg/day) for an 8-week recovery duration. Long-term PCB138 exposure resulted in elevated liver/body weight ratio, hepatic triglyceride/cholesterol accumulation, and histopathological lipidosis, confirming MAFLD progression. Mechanistically, chronic oral exposure to PCB138 induced multi-organ dysregulation, characterized by: (i) intestinal barrier disruption, (ii) gut microbiota dysbiosis, (iii) disruption of the gut-liver bile acid axis accompanied by hepatic accumulation of lithocholic acid (LCA), taurolithocholic acid (TLCA), taurodeoxycholic acid (TDCA), and glycodeoxycholic acid (GDCA), and (iv) upregulated hepatic fatty acid synthase (FASN) expression, thereby accelerating de novo lipogenesis. TB administration for another 8 weeks attenuated these MAFLD manifestations, eviden...