Lead Exposure Induces Weight Gain in Adult Rats, Accompanied by DNA Hypermethylation.

Abstract

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. 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. 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. Pb exposure resulted in dose-specific weight gain in adult Wistar rats, accompanied by alteration of DNA methylation.