title: DEHP induces obesity and hypothyroidism through both central and peripheral pathways in C3H/He mice.
abstract: OBJECTIVE
  Di(2-ethylhexyl) phthalate (DEHP) is reported to cause obesity and hypothyroidism in both humans and rodents, but the underlying mechanisms were largely unknown. This study was designed to clarify the effects and the mechanisms of DEHP on the pathogenesis of obesity and hypothyroidism and to discover the relationship between them.
  
  
  METHODS
  Male C3H/He mice were treated with DEHP for 5 weeks, and the body weight, food intake, and body temperature were recorded during the exposure. After exposure, key organs and serum were analyzed by Q-PCR, Western blot, and ELISA.
  
  
  RESULTS
  DEHP induced significant body weight gain and adipogenesis in all exposure groups except for 0.05 mg/kg. Marked hyperphagia and daytime hypothermia were also observed, which were accompanied by disturbed hypothalamic neuropeptide expression and reduced BAT UCP1 expression. In addition, WAT lipid metabolism was significantly deceased at low dose (0.5 mg/kg) and increased at high dose (50 and 200 mg/kg). DEHP also induced hypothyroidism, which was probably attributed to the combined effects of hepatic CAR activation and hypothalamic TRH inhibition induced by hypothalamic leptin resistance.
  
  
  CONCLUSIONS
  Chronic DEHP exposure could induce obesity by interrupting energy homeostasis, which is probably due to the synergistic effects of hypothyroidism and hypothalamic leptin resistance.
authors.affiliation: Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Ziquan
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Suli
authors.initials: S
authors.lastname: Huang
authors.affiliation: Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Yangshen
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Guanqin
authors.initials: G
authors.lastname: Huang
authors.affiliation: Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
authors.affiliation: Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Shiquan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.affiliation: Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Yuebin
authors.initials: Y
authors.lastname: Ke
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D001835:Body Weight; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000009:adverse effects*; D007031:Hypothalamus / Q000378:metabolism*; D007037:Hypothyroidism / Q000139:chemically induced* / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009765:Obesity / Q000139:chemically induced* / Q000378:metabolism; D010968:Plasticizers / Q000008:administration & dosage / Q000009:adverse effects*; D060888:Real-Time Polymerase Chain Reaction; D015430:Weight Gain / Q000187:drug effects
chemical_list: D020738:Leptin; D010968:Plasticizers; D004051:Diethylhexyl Phthalate