TCDD induced lipid accumulation by impairment of autophagic flux in THP-1 macrophages.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental and food contaminant generated as a byproduct of various industrial activities. It is found in a lot of foods, especially in dairy products, eggs, fish, and meat. Autophagy is a highly conserved cellular degradation and cycling process, which plays an important role in lipid metabolism. This study aimed to explore the effects of TCDD on autophagic flux and lipid metabolism in THP-1 macrophages. The data showed that TCDD promoted the accumulation of autophagosomes in THP-1 macrophages, and subsequent findings revealed that this autophagosome accumulation was caused by the inhibition of autophagic flux by testing the expression of LC3II, p62 levels, and mRFP-GFP-LC3. Further, we found that TCDD treatment significantly increased the amount of triglyceride (TG) and total cholesterol (TC) in THP-1 macrophages. Meanwhile, pretreatment with autophagy activator (rapamycin, Rapa) efficiently relieved TCDD-induced lipid accumulation. On the contrary, pretreatment with autophagy inhibitor (Chloroquine, CQ) promoted TCDD-induced lipid accumulation. In the experiment of co-localization of LC3 and lipid droplets, the co-localization of LC3 and lipid droplets increased after TCDD induction. These results indicated that TCDD promoted lipid accumulation in THP-1 macrophages by inhibiting autophagic flux. Our findings revealed new insights into the toxicity mechanisms of TCDD.