Establishment of the rat model of metabolic syndrome and study of gender differences in glucose and lipid metabolism in placenta and adult individuals
Objective:To construct an experimental animal model of metabolic syndrome(MS)and to explore the sexual dimorphism of glucose and lipid metabolism abnormalities in both placenta and adult individuals.Methods:The rat model of gestational metabolic syndrome(GMS)was induced by a high-calorie diet plus 5％fructose water.Sixteen female Wistar rats were randomly divided into two groups as the control group(normal diet and water,NC group,n=8)and GMS group(high-calorie diet and 5％fructose drinking water,HDF5 group,n=8).And there are 14 female rats and 14 male rats were randomly and respectively divided into two groups as female MS group(F-HDF5 group,n=7),male MS group(M-HDF5 group,n=7),and both control groups with normal diet and water intake(F-NC group,n=7,M-NC group,n=7).The body weight(weight),systolic blood pressure(SBP)and diastolic blood pressure(DBP)of the rats in each group were monitored and recorded weekly from baseline(W0)after 1 week of adaptation to the 5th week of diet/water intervention(W5).Fasting blood glucose(FBG)levels were detected on W0 and W5,and oral glucose tolerance test(OGTT)was performed.Fasting serum was collected for detection of triglyceride(TGs)and total cholesterol(T-CHO)concentrations.Fasting serum and liver tissues of male and female MS rat models were collected in W5,and fetal mice and placenta tissues were collected at 20.5 days of gestation(GD20.5),and concentrations of TGs and T-CHO,lipoprotein lipase(LPL)activity and free fatty acid(FFA)content of placenta tissues were detected.The placenta tissues were subjected to HE staining and Oil Red O staining.Results:After 5 weeks of diet/water intervention,the measured values of body weight(P＜0.001)and body mass index(BMI,P＜0.05),FBG(P＜0.001)and the area under the receiver operating characteristic curve(AUC,P＜0.05),TGs and T-CHO(P＜0.001),SBP(P＜0.001)and DBP(P＜0.05)in the HDF5 group were significantly increased,suggesting that the female rat GMS model was successfully constructed,and the blood pressure was increased during pregnancy(P＜0.05).At GD20.5,the HDF5 group showed significant increases in the levels of FBG,TGs and T-CHO(P＜0.001),the weight of the placenta of the rats with male offspring was significantly increased(P＜0.01).The LPL activity of placentas of the rats with male and female offspring was significantly decreased(P＜0.01),and the contents of TGs,T-CHO and FFA were significantly increased(P＜0.05).The contents and lipid droplets in placentas of rats with male offspring were significantly higher than those with female offspring(P＜0.05).In adult male and female rat MS models,after 5 weeks of intervention,except for the BMI of M-HDF5(P＞0.05),other MS-related indicators were significantly increased in F-HDF5 and M-HDF5(P＜0.05).F-HDF5 showed a more significant increase in blood glucose(P＜0.05),while M-HDF5 showed a more significant elevation in blood lipid parameters(P＜0.05).The liver weight and FFA content of rats in both groups were significantly increased(P＜0.05),and the enzyme activity of LPL was significantly decreased in F-HDF5 and significantly increased in M-HDF5(P＜0.05).Conclusions:A high-calorie diet and 5％fructose water intake can induce the metabolic syndrome phenotype in male and female rats within five weeks.The dysregulation of glucose and lipid metabolism is evident in both the placenta and adult individuals,exhibiting sex-specificity differences as well as organ-specificity.
Gestational metabolic syndromeAbnormal glucose and lipid metabolismGender differenceModeling method
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