Background: In the last decades, the prevalence of diabetes and related diseases of metabolic disorders has a dramatic increase. The global prevalence of diabetes and its related diseases is closely associated with the exposure to polychlorinated biphenyls (PCBs).

Aim: To investigate the the effect of PCB-126 on glucose/lipid metabolism and hepatic steatosis and to elucidate the molecular mechanisms.

Methods: C57BL/6J mice were orally administrated with PCB-126 (1.5 mg/kg) twice in a week with or without the injection of GDC-0941 (1 mg/kg) before the administration of PCB-126. The experimental period was two weeks.

Results: PCB-126 significantly decreased fasting blood glucose level, reduced glucose levels in the glucose and insulin tolerance tests, indicating that PCB-126 treatment increased insulin sensitivity in mice. In addition, PCB-126 exposure resulted in a significant increase in hepatic lipid content, as reflected by biochemical determination, Oil Red O staining and Bodipy staining. Using transmission electron microscope, we observed that PCB-126 increased the number and size of lipid droplets in liver tissues. We showed that injection of GDC-0941, an inhibitor of insulin signaling, slightly inhibited the effect of PCB-126 on glucose levels and glucose and insulin tolerance. Although GDC-0941 did not significantly affect the content of triglyceride in liver of PCB-126-treated mice, the size of hepatic lipid droplet was significantly reduced by GDC-0941, as evidence by Bodipy staining and observation under transmission electron microscope. Moreover, PCB-126-induced expression of aryl hydrocarbon receptor and lipogenesis-related regulators, such as sterol regulatory element-binding protein 1, was inhibited by GDC-0941.

Conclusion: The data suggest that enhancement of insulin sensitivity contributes to PCB-126-induced hepatic steatosis and injury.


X. Wang: None.

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