Intrauterine Metabolome Characteristics Of Glucose Metabolism Disorder Caused By Maternal Lipopolysaccharide Exposure In Male Offspring And Protection Of Vitamin D

Background The incidence of diabetes is increasing,and it is critical to explore the pathogenesis of diabetes and to develop prevention strategies.The developmental origins of health and disease(DoHaD)focuses on the close relationship between chronic diseases and early life healthy,and provides ideas for nursing staff to carry out primary prevention of diabetes.Exposure to lipopolysaccharide(LPS)is one of the factors that can not be ignored during pregnancy.The previous study found that the exposure to low-dose LPS during pregnancy can lead to glucose metabolism disorder in adult male offspring,but its intrauterine mechanism and metabolic changes need to be further explored.Metabolomics is useful for exploring the mechanisms of disease and screening for potential biomarkers for early screening and risk warning.Therefore,the present study was based on metabolomics to explore the intrauterine mechanism and early metabolic changes of diabetes during early life.It is helpful for nurse to identify early warning of diabetes in early life.In addition,vitamin D is anti-inflammatory,but it is still unclear whether vitamin D could change the abnormal metabolism in the intrauterine stage caused by maternal LPS exposure.This study will initially explore the protective effect of vitamin D supplementation on maternal and male offspring.It is helpful for nurses to carry out nutritional health education and guide pregnant women to supplement vitamin D during pregnancy.Objective The aims of the present study were to analyze of the effects of LPS exposure on maternal and offspring metabolism and to explore the intrauterine mechanism of glucose metabolism disorder in male offspring.Furthermore,we also investigated the protection of VD on maternal and male offspring metabolism after maternal exposed to LPS.Methods Pregnant mice were randomly divided into three groups,control group,LPS group and LPS+vitamin D group.The LPS group was intraperitoneally injected with LPS(50ug/kg/d)and intragastrically administered with phosphate buffered saline from gestational day(GD)15 to GD 17.The LPS+ vitamin D group were intraperitoneally injected with LPS at 50ug/kg/d and intragastrically administered with Vitamin D(25?g/kg).The control group was intraperitoneally injected with the same dose of normal saline.In the morning of GD18,the pregnant mice were killed,the fetuses were taken and were weighed.The metabolic profiles of maternal serum and male fetal liver were analyzed using Liquid Chromatograph Mass Spectrometer(LC-MS)techniques.The effects of LPS exposure during pregnancy on maternal and male fetal metabolomes were analyzed by comparing differential metabolites between LPS and CON groups.The effects of vitamin D supplementation on the maternal and male fetal metabolomes after LPS exposure were analyzed by comparing the differential metabolites of LPS+vitamin D group and LPS group.Results(1)After LPS exposure,38 metabolites in the maternal serum were altered,mainly including fatty acids and glycerophospholipids.In glycerophospholipids,glycerophospholipids containing saturated fatty acids are up-regulated,and glycerophospholipids containing polyunsaturated fatty acids are down-regulated.In fatty acids,stearic acid,palmitic acid,oleic acid,8,11,14-eicosatrienoic acid and3-dehydroxycarnitine are up-regulated,and docosahexaenoic acid(DHA)is down-regulated.(2)After LPS exposure,75 metabolites in the fetal liver were altered.Interestingly,the alteration of glycerophospholipids in the fetal liver are similar to those of the mother.In fatty acids,stearic acid,ceramide carnitine,isobutyryl-L carnitine and stearyl carnitine are up-regulated.Moreover,DHA,eicosapentaenoic acid(EPA),epoxy eicosatrienoic acid,?-linolenic acid and linoleic acid are lowered.(3)After vitamin D supplementation,10 metabolites in the pregnant mice induced by LPS were changed,including glycerophospholipids,DHA and 3-dehydroxycarnitine were altered.Moreover,DHA,EPA,5,6-Epoxy-8,11,14-eicosatrienoic acid epoxy,linoleic acid,and cervonyl carnitine in fetal liver were changed.Conclusions(1)Low-dose LPS exposure during pregnancy interferes with the normal metabolic pathways of maternal and male offspring,including glycophospholipids and fatty acid metabolism.(2)After LPS exposure,glycerophospholipids containing saturated fatty acids were up-regulated,and glycerophospholipids containing polyunsaturated fatty acids were down-regulated.In addition,LPS-exposed dams also had increased saturated fatty acids levels and decreased polyunsaturated fatty acids levels in pregnant mice.(3)Intrauterine metabolic changes associated with adult glucose metabolism disorders caused by low-dose LPS exposure during pregnancy are mainly characterized by up-regulation of saturated fatty acid-contained glycerophospholipids and down-regulation of polyunsaturated fatty acid-contained glycerophospholipids.Up-regulation of saturated fatty acids and acylcarnitines and down-regulation of polyunsaturated fatty acids such as DHA and EPA in fatty acids maybe another mechanism.(4)Low-dose LPS exposure during pregnancy could lead to similar metabolic changes in pregnant mice and male offspring.(5)Vitamin D supplementation can partially change the metabolic abnormalities of maternal and male offspring.In the pregnant mice,some glycophospholipids composed of saturated fatty acid chains are down-regulated and DHA is up-regulated after vitamin D supplementation.In male offspring,vitamin D supplement changed fatty acid metabolism.