Polychlorinated biphenyls (PCBs) are persistent organic pollutants found in various environmental media, and there is growing evidence that PCBs may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The purposes of this study were to investigate whether environmental level of Aroclor 1254 (a commercial mixture of PCBs) exposure to adolescent male mice could induce the development of NAFLD and the mechanisms involved. Twenty-one-day-old male C57BL/6 mice were exposed to Aroclor 1254 (0.5-500 μg/kg body weight) by oral gavage once every third day for 60 days. The results showed that exposure to Aroclor 1254 increased body weight and decreased the liver-somatic index in a dose-dependent manner. Aroclor 1254 administration increased lipid accumulation in the liver and induced the mRNA expression of genes associated with lipogenesis, including acetyl-CoA carboxylase 1 (Acc1), acetyl-CoA carboxylase 2 (Acc2) and fatty acid synthase (Fasn). Moreover, Aroclor 1254 decreased peroxisome proliferator-activated receptor alpha (PPARα) signaling and lipid oxidation. In addition, we found that Aroclor 1254 administration induced oxidative stress in mouse liver and elevated the protein level of cyclooxygenase 2 (COX-2), an inflammatory molecule, possibly via the endoplasmic reticulum (ER) stress inositol-requiring enzyme 1α-X-box-binding protein-1 (IRE1α-XBP1) pathway, but not the nuclear factor-κB (NF-κB) pathway. In summary, adolescent exposure to environmental level of PCBs stimulated oxidative stress, ER stress and the inflammatory response and caused NAFLD in male mice. This work provides new insight into the idea that adolescent exposure to environmental level of PCBs might induce the development of NAFLD under the regulation of ER stress in males.
Keywords: Endoplasmic reticulum stress; Inflammation; Lipid metabolism; Non-alcoholic fatty liver disease; Polychlorinated biphenyls.
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