title: Lead Exposure Induces Weight Gain in Adult Rats, Accompanied by DNA Hypermethylation.
abstract: OBJECTIVE
  Previous studies have revealed the association of lead (Pb) exposure with obesity. DNA methylation alteration has been suggested to be one of the regulatory mechanisms of obesity. We aimed to explore whether Pb exposure is related with weight gain and DNA methylation alteration.
  
  
  METHODS
  Male adult 8 week Wistar rats were divided into 5 groups: the normal chow diet (NCD); the NCD+0.05%Pb; the NCD+0.15%Pb; the NCD+0.45%Pb and the high fat diet. Rats were exposed to different dosages of Pb through drinking water for 21 weeks. Body weight, fasted blood glucose level, fasted insulin level, homeostasis assessment of insulin resistance (HOMA-IR) index and lipid profile were detected. Intra-peritoneal glucose tolerance test (IPGTT) was constructed to evaluate the glucose tolerance. Lipid accumulation of liver was detected and liver DNA underwent whole genome bisulfite sequencing.
  
  
  RESULTS
  The NCD+0.05%Pb group had significantly greater weight, HOMA-IR and triglycerides, and lower glucose intolerance than the NCD group (P <0.05). This group also showed hepatic lipid accumulation. These metabolic changes were not observed in the other two Pb dosage groups. Furthermore, DNA hypermethylation extended along pathways related to glucose and lipid metabolism in NCD+0.05%Pb group.
  
  
  CONCLUSIONS
  Pb exposure resulted in dose-specific weight gain in adult Wistar rats, accompanied by alteration of DNA methylation.
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Sun
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Ningjian
authors.initials: N
authors.lastname: Wang
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Nie
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cang
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Chen
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Lu
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Hualing
authors.initials: H
authors.lastname: Zhai
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Fangzhen
authors.initials: F
authors.lastname: Xia
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D007854:Lead / Q000633:toxicity*; D050356:Lipid Metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics
chemical_list: D001786:Blood Glucose; D007854:Lead