The Mechanism Of Lead Exposure On Regulation Of Lipid Homeostasis In Rats

Objective: Our previous epidemiological study on environmental pollution revealed that lead may be a risk factor for Chinese adult obesity.On this basis,we carried out animal experiments,to establish a rat model of different concentrations of lead exposure as well as in vitro experiments with 3T3L1 preadipocyte to explore lipid metabolism changes and possible mechanism.Materials and Methods: 8 weeks SPF grade 25 Wistar rats were randomly divided into 5 groups: normal control group: NCD(treated with normal drinking water);NCD+0.05%Pb group(treated with 0.05% lead acetate water);NCD+0.15%Pb group(treated with 0.15% lead acetate water);NCD+0.45%Pb group(treated with 0.45% lead acetate water);high fat group: HFD(treated with normal drinking water).21 weeks after lead acetate drinking,the IPGTT was administrated in order to compare glucose tolerance level.In addition,serum insulin levels,HOMA-IR index,blood lipid levels were determined.Liver tissues were stained to detect the level of lipid deposition.Whole genome bisulfite sequencing were taken to detect the change of DNA methylation level.Lead acetate were administrated during the differentiation of 3T3L1 preadipoctye.The expression of differentiation related genes such as PPARγand C/EBP were detected.Oil red staining was constructed in order to evaluate differential level.Results: 1.Body lead levels,body weight: 21 weeks after modeling,the bone lead depositions in rats with lead exposure were in accordance with the gradient of lead concentration in drinking water.NCD+0.05% lead exposed rats gained more weight compared with NCD control group(P<0.05).2.Blood glucose levels,IPGTT tests: The fasted blood glucose levels of each lead exposed group were not significantly increased compared to the control group.IPGTT test indicated that the NCD+0.05% lead exposed rats appeared abnormal glucose tolerance,with significantly increased AUC level(P<0.05);elevated blood insulin levels and increased HOMA-IR index(P<0.05);3.Blood lipid levels,liver oil red staining and hematein eosin staining: The blood TG level,blood LDL-C were increased in NCD+0.05% lead exposed group(P<0.05).In addition,liver oil red staining showed liver lipid deposition.4.Tissue DNA methylation detection: The whole genome DNA methylation sequencing of liver revealed hypermethylation of whole genome in NCD+0.05% lead exposed rats compared with NCD rats.5.In vitro experiments with 3T3L1 preadipocyte:Lead acetate promoted the process of differentiation of 3T3L1 cells,improved the expression of adipogenesis related genes as well as lipid deposition.Conclusions: Pb exposure resulted in lipid disorder in adult Wistar rats,accompanied by alteration of DNA methylation.Pb exposure promoted adipogenesis in 3T3L1 cells.