Hepatic AhR Activation by TCDD Induces Obesity and Steatosis via Hepatic Plasminogen Activator Inhibitor-1 (PAI-1).

ABSTRACT: Exposure to persistent organic pollutants such as 2,3,7,8-tetrachlorodibenzodioxin (TCDD) increases metabolic disorder risk. In this study, we show that a single intraperitoneal injection of TCDD (10 μg/kg) in C57BL/6J mice induced body weight gain, lipid accumulation in the liver and adipose tissue, macrophage infiltration, and elevated hepatic and serum triglyceride levels after 12 weeks. Despite serum aryl hydrocarbon receptor (AhR) ligand levels normalizing by 12 weeks, the persistent effects suggest TCDD sequestration in fat tissue. TCDD inhibited the expression of mitochondrial proteins (COX1, TOM20, TFAM, H2AX) and reduced mitochondrial oxygen consumption. Liver-specific AhR knockout ameliorated TCDD-induced mitochondrial dysfunction, lipid accumulation, and macrophage infiltration.

SUBMITTER: Oh SJ 

PROVIDER: S-EPMC12428968 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature