Effects of Di-(2-ethylhexyl) Phthalate on Lipid Metabolism by the JAK/STAT Pathway in Rats

The most widely used plasticizer, di-(2-ethylhexyl) phthalate (DEHP), is known to affect lipid metabolism and adipogenesis. We studied the effects of dietary DEHP exposure on metabolism in rats as well as the role of the JAK/STAT pathway in this process. Eighty rats were exposed to DEHP (0, 5, 50 and 500 mg/kg/d) through dietary intake for 4 weeks. We then collected blood samples, liver, and adipose tissues to detect modifications in the levels of serum lipids, leptin, adiponectin and insulin. JAK3, STAT5a and PPARγ expression were detected at both the gene and protein levels. The activation of JAK3 and STAT5a was also detected. The DEHP-exposed rats had increased body weight, serum lipid, insulin, and leptin levels. Moreover, the JAK3/STAT5a pathway was activated in the adipose tissue; however, this pathway was not activated in the liver. The mRNA of SREBP-1c in the liver was increased significantly among each of the groups, in contrast to the levels found in the mature SREBP-1c protein form. Furthermore, the expression of FABP4, Acox and FASn was decreased in the liver, but increased in adipose tissue. Thus, we conclude that exposure to DEHP reduces the hydrolysis of lipid and promotes triglyceride accumulation by oppositely regulating the activation state of JAK/STAT pathway in the liver and adipose tissue, resulting in the disorder of body lipid metabolism and obesity.