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 ofFABP4,AcoxandFASnwas 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.
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. jiayy14@mails.jlu.edu.cn.
Yiyang
Y
Jia
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. iamliute@126.com.|Scientific Research Center, China-Japan Union Hospital, Jilin University, Changchun 130033, China. iamliute@126.com.
Te
T
Liu
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. zhoulttg@163.com.
Liting
L
Zhou
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. zhujian@mails.jlu.edu.cn.
Jian
J
Zhu
Cancer Center, Tumor Hospital of Jiangxi Province, Nanchang 330029, China. wujuan13@mails.jlu.edu.cn.
Juan
J
Wu
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. s184349549@live.com.
Di
D
Sun
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. xujin14@mails.jlu.edu.cn.
Jin
J
Xu
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. wangqi15@mails.jlu.edu.cn.
Qi
Q
Wang
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. chenhj15@mails.jlu.edu.cn.
Huaiji
H
Chen
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. xufeng15@mails.jlu.edu.cn.
Feng
F
Xu
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. s418824079@126.com.
Yuezhu
Y
Zhang
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. zhangtr16@mails.jlu.edu.cn.
Tianrong
T
Zhang
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. liuhb@mails.jlu.edu.cn.
Hongbo
H
Liu
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China. jlyelin@163.com.
Lin
L
Ye
D000818:Animals; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D010968:Plasticizers / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004785:Environmental Pollutants; D010968:Plasticizers; D050791:STAT Transcription Factors; D014157:Transcription Factors; D004051:Diethylhexyl Phthalate
JAK/STAT; adipose tissue; di-(2-ethylhexyl) phthalate; lipid metabolism