Environmental pollutants BDE-47 exposure and its impact on metabolism in prediabetic mice
Objective Investigate the effects of 2,2',4,4'-tetrabromodiphenyl ether(BDE-47)exposure on metabolism in pre-diabetic mice,reveal its potential metabolic toxicity.Methods In this study,24 male SPF C57BL/6J mice were randomly divided into four groups with 6 mice in each group:control group,model group,BDE-47 medium dose group and BDE-47 high dose group.In addition to the control group,the other groups were given a high-sugar and high-fat diet and streptozotocin injection to establish a prediabetes model.After the establishment of the prediabetes model,BDE-47 medium dose group and BDE-47 high dose group were given 50 and 100 mg/kg BDE-47,respectively;control group and model group were given equal volume of corn oil for 8 weeks.The mice were killed and blood and tissue samples were collected.Fasting blood glucose,2 h postprandial blood glucose and serum insulin were measured.The pathological conditions of colon and intestinal tissues were observed by hematoxylin-eosin(HE)staining.Non-targeted metabolomics was used to analyze the changes of metabolites.Results After 8 weeks of gavage,there were significant differences in fasting blood glucose,2-hour postprandial glucose,fasting insulin and the insulin β-cell index in four groups(F=11.091,5.377,3.698,15.143;all P＜0.05).HE staining results showed significant atrophy of the small intestinal villi in the middle and high dose groups of BDE-47,structural loss,loss of the crypt part,and decreased height of the small intestinal villi,along with inflammatory cell infiltration,showing some degree of tissue damage.Non-targeted metabolomics revealed that,compared to the model group,differential metabolites in the BDE-47 high-dose group were primarily enriched in a broad range of metabolic pathways.The BDE-47 medium-dose group showed significant enrichment of differential metabolites in aldosterone-regulated sodium reabsorption and steroid hormone biosynthesis pathways.Network analysis indicated that phosphatidylglycerol metabolism was a central pathway in the BDE-47 high-dose group,whereas cholesterol metabolism was central pathway in the medium-dose group.Conclusions BDE-47 not only elevated fasting and postprandial blood glucose in prediabetic mice,but also led to changes in key metabolites and pathways,particularly those involved in phospholipid metabolism,which might contribute to the development of diabetes.The effects of BDE-47 on metabolites in prediabetic mice suggest that environmental pollutants could influence diabetes development by altering metabolite levels.
NETL
NSTL
万方数据
