不同类型母体肥胖对新生子代大鼠糖脂代谢的影响和机制研究

Effects and mechanisms of different types of maternal obesity on glucose and lipid metabolism in neonatal offspring rats

目的探讨大鼠孕前肥胖(pre-pregnancy obesity, PO)、孕期增重过多(excessive gestational weight gain, EGWG)、孕前肥胖合并孕期增重过多(PO+EGWG)对新生子代糖脂代谢的影响及可能机制。方法通过不同时期高脂饲料喂养SD大鼠, 构建PO、EGWG、PO+EGWG动物模型。36只SD大鼠随机分为4组, 每组9只。对照组孕前、孕期均正常饮食, PO组孕前高脂饮食、孕期正常饮食, EGWG组孕前正常饮食、孕期高脂饮食, PO+EGWG组孕前、孕期均高脂饮食。记录母鼠孕前、孕期体重及新生仔鼠出生体重。取雄性新生仔鼠, 每组9只, 血糖仪检测空腹血糖水平, 酶联免疫吸附试剂盒检测空腹胰岛素水平, 甘油磷酸氧化酶-过氧化物酶法检测肝脏甘油三酯、胆固醇水平, 苏木精-伊红染色、油红O染色观察肝脏脂质沉积, 逆转录-聚合酶链反应检测肝脏糖代谢通路关键基因IR、IRS、AKT及脂质代谢关键基因FASN、SREBP1c、PPARα的mRNA水平。结果孕前高脂饮食组(PO组、PO+EGWG组)母鼠孕前体重高于孕前正常饮食组(对照组、EGWG组), 孕期高脂饮食组(EGWG组、PO+EGWG组)母鼠孕期增重百分比高于孕期正常饮食组(对照组、PO组), 差异有统计学意义(P<0.05)。PO组、EGWG组、PO+EGWG组新生仔鼠出生体重均高于对照组, PO+EGWG组高于PO组和EGWG组, 差异有统计学意义(P<0.05);PO组、EGWG组、PO+EGWG组新生仔鼠空腹血糖、胰岛素水平及胰岛素抵抗指数虽高于对照组, IR、IRS、AKT的mRNA水平低于对照组, 但差异均无统计学意义(P>0.05);EGWG组和PO+EGWG组肝脏甘油三酯、胆固醇含量及FASN、SREBP1c的mRNA水平均高于对照组, PO+EGWG组PPARα的mRNA水平高于对照组和PO组, 差异有统计学意义(P<0.05)。结论分别在孕前、孕期和孕前孕期高脂饲料喂养SD大鼠, 可成功构建PO、EGWG、PO+EGWG动物模型。PO+EGWG对新生子代大鼠出生体重及糖脂代谢影响最显著, 与EGWG相比, PO对新生子代大鼠糖代谢影响相对显著, EGWG对新生子代大鼠脂代谢影响相对显著。母体肥胖对子代大鼠糖脂代谢的影响考虑与糖脂代谢基因的表达改变有关。

Objective To study the different effects of pre-pregnancy obesity(PO),excessive gestational weight gain(EGWG),pre-pregnancy obesity combined with excessive gestational weight gain(PO+EGWG)of maternal rats on glucose and lipid metabolism in neonatal offspring,and to explore the possible mechanisms.Methods Animal models of PO,EGWG and PO+EGWG were established by feeding SD rats with high-fat diets at different periods.Thirty-six SD rats were randomly divided into four groups,with nine rats in each group.The control group had a normal diet before and during pregnancy.The PO group had a high-fat diet before pregnancy and a normal diet during pregnancy.The EGWG group had a normal diet before pregnancy and a high-fat diet during pregnancy.And the PO+EGWG group had a high-fat diet before and during pregnancy.The body weight of maternal rats before and during pregnancy and the birth weight of neonatal rats were recorded.Nine male neonatal rats in each group were selected,fasting blood glucose levels were detected by glucometer,fasting insulin levels were detected by enzyme-linked immunosorbent assay kit,hepatic triglyceride and cholesterol levels were detected by glycerol phosphate oxidase-peroxidase method,hepatic lipid deposition were observed by hematoxylin-eosin staining and oil red O staining.The mRNA levels of hepatic key genes in glucose metabolism pathway IR,IRS,AKT and lipid metabolism FASN,SREBP1c,PPARαwere detected by reverse transcription-polymerase chain reaction analyses.Results The pre-pregnancy weight of maternal rats in high-fat diet group before pregnancy(PO group and PO+EGWG group)was significantly higher than those in normal diet group(control group and EGWG group).The percentage of weight gain of maternal rats in high-fat diet group during pregnancy(EGWG group and PO+EGWG group)was significantly higher than those in normal diet group(control group and PO group)(P<0.05).The birth weight of neonatal rats in PO group,EGWG group and PO+EGWG group were significantly higher than that in control group(P<0.05),and the birth weight of neonatal rats in PO+EGWG group was the largest.The fasting glucose,insulin level and insulin resistance index of newborn rats in PO,EGWG and PO+EGWG groups were higher than those in the control group,and the mRNA levels of IR,IRS and AKT were lower than those in the control group,but the differences were not statistically significant(P>0.05).The hepatic triglyceride and cholesterol contents and mRNA levels of FASN and SREBP1c were higher in the EGWG and PO+EGWG groups than those in the control group,and the mRNA level of PPARαwas higher in the PO+EGWG group than in the control and PO groups,with statistically significant differences(P<0.05).Conclusions Animal models of PO,EGWG and PO+EGWG were successfully constructed by feeding SD rats with high-fat diets before pregnancy,during pregnancy,before and during pregnancy.PO+EGWG had the most significant effects on the birth weight and glucose and lipid metabolism in neonatal offspring.Compared with EGWG,PO had a relatively significant effect on glucose metabolism in neonatal offspring.And compared with PO,EGWG had a relatively significant effect on lipid metabolism in neonatal offspring.The effects of maternal obesity on glucose and lipid metabolism in neonatal offspring were considered to be related to the expression changes of genes in glucose and lipid metabolism.