Abstract
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.
Highlights
The most widely used plasticizer, di-(2-ethylhexyl) phthalate (DEHP), is known to cause reproductive toxicity and possesses endocrine disruptive potential [1,2]
We further examined the phosphorylated state of the proteins and found that the activated state (Figure 5B) in the 50 mg/kg/d and 500 mg/kg/d DEHP group were significantly lower than activated of JAK3 (Figure 5B) in the 50 mg/kg/d and 500 mg/kg/d DEHP group were significantly lower than state observed in the 5 mg/kg/d DEHP and control group (p < 0.05)
The dose-response relationship was not observed in the adipose tissue, where we only detected significantly increased mRNA levels of JAK3 and STAT5a in the 500 mg/kg/d DEHP group. These results suggest that the gene expression of JAK3 and STAT5a is up-regulated after exposure to DEHP; the regulation of DEHP dose varies among different tissues
Summary
The most widely used plasticizer, di-(2-ethylhexyl) phthalate (DEHP), is known to cause reproductive toxicity and possesses endocrine disruptive potential [1,2]. This synthetic chemical is known to be an endocrine-disrupting chemical, which are known to adversely affect the endocrine system, and can be found in a variety of plastic products, household paints, as well as toys used by children. Human exposure to DEHP is reported to be mainly through ingestion and dermal contact [3]. A number of studies have shown that exposure to DEHP can cause abnormal lipid metabolism in humans, which results in numerous health implications such as heart disease, diabetes, and as the most common disorder, obesity [4,5,6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: International Journal of Environmental Research and Public Health
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
