孕前肥胖、孕期过度增重对子代代谢特征的影响及机制

Effects of obesity before pregnancy and excessive weight gain during pregnancy on the characteristics of offspring metabolism and the underlying mechanism

目的探讨孕前肥胖、孕期过度增重对子代代谢特征的影响及机制。方法选择2016年4月至2018年12月在嘉兴市第二医院和嘉兴市秀洲区妇幼保健院住院分娩且签署知情同意书的孕妇及分娩的单胎新生儿为研究对象,经筛选后共有2000例孕妇及其新生儿进入该次的研究中。按照孕妇的孕前、孕期体质量分为研究组与对照组。对照组1576例孕妇均为孕前、孕期体质量正常的孕妇,观察组424例为孕前、孕期体质量超重的孕妇。比较两组新生儿瘦素、血脂、血糖(FBG)、胰岛素水平(FINS)及下丘脑瘦素受体(OB-Rb)、细胞因子信号转导抑制因子3(SOCS3)基因表达、胰岛素抵抗指数(IRI)、胰岛素敏感指数(ISI)等。结果研究组孕妇孕前体质量指数和孕期体质量[(30.91±1.86)kg/m2和(21.25±2.61)kg]增加明显高于对照组[(26.87±1.05)kg/m2,(14.57±1.36)kg],差异均有统计学意义(t=7.972,P=0.013;t=9.786,P=0.001)。研究组新生儿瘦素、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)水平[(1.23±0.29)ng/mL,(0.65±0.16)mmol/L,(1.40±0.24)mmol/L,(0.76±0.13)mmol/L]均明显高于对照组[(0.63±0.11)ng/mL,(0.38±0.16)mmol/L,(1.13±0.32)mmol/L,(0.56±0.09)mmol/L],且高密度脂蛋白(HDL-C)水平[(1.26±0.17)mmol/L]明显低于对照组[(1.75±0.26)mmol/L],两组差异均有统计学意义(t=7.701,P=0.010;t=7.329,P=0.019;t=5.734,P=0.030;t=9.387,P=0.001;t=8.072,P=0.008)。研究组新生儿SOCS3mRNA、OB-RbmRNA表达[(1.44±0.29),(1.33±0.39)]均明显高于对照组[(0.33±0.19),(0.50±0.21)],两组差异有统计学意义(t=9.987,P<0.001;t=11.037,P<0.001)。研究组的FBG、FINS水平[(22.06±3.94)mmol/L,(20.02±4.61)mU/L]明显高于对照组[(11.73±2.92)mmol/L,(13.31±3.43)mU/L],IRI(19.79±6.29)明显高于对照组(6.96±2.52),而ISI(-6.07±0.32)明显低于对照组(-4.98±0.37),两组差异均有统计学意义(t=8.133,P=0.001;t=4.498,P=0.027;t=7.352,P=0.002;t=8.244,P<0.001)。结论孕前肥胖与孕期过度增重会提高SOCS3基因的表达水平,进一步影响子代STAT3-SOCS3-瘦素/胰岛素信号通路的表达。

Objective To investigate the effects of obesity before pregnancy and excessive weight gain during pregnancy on the characteristics of offspring metabolism and the underlying mechanism.Methods Pregnant women who delivered from April 2016 to December 2018 in Jiaxing Xiuzhou District Maternal and Child Health Hospital after providing written informed consent and their singleton newborns were considered for recruitment for this study.Finally,2000 pregnant women and their newborns were included in this study.These pregnant women were divided into study control(n=1576,normal body weight)and(n=424,overweight)groups according to their body mass before and during pregnancy.The levels of leptin,blood lipid,fasting blood glucose,fasting insulin,long form of leptin receptor(OB-Rb),suppressor of cytokine signaling 3(SOCS3)gene expression,insulin resistance index,and insulin sensitivity index were compared between the control and study groups.Results The body mass index before pregnancy and body mass during pregnancy in the study group were(30.91±1.86)kg/m2 and(21.25±2.61)kg,respectively,which were significantly higher than those in the control group[(26.87±1.05)kg/m2,(14.57±1.36)kg,t=7.972,P=0.013;t=9.786,P=0.001].The levels of leptin,triglyceride,total cholesterol and low-density lipoprotein cholesterol in the study group were(1.23±0.29)ng/mL,(0.65±0.16)mmol/L,(1.40±0.24)mmol/L,(0.76±0.13)mmol/L,respectively,which were significantly higher than those in the control group[(0.63±0.11)ng/mL,(0.38±0.16)mmol/L,(1.13±0.32)mmol/L,(0.56±0.09)mmol/L,t=7.701,P=0.010;t=7.329,P=0.019;t=5.734,P=0.030;t=9.387,P=0.001].The level of high-density lipoprotein cholesterol in the study group was significantly lower than that in the control group[(1.26±0.17)mmol/L vs.(1.75±0.26)mmol/L,t=8.072,P=0.008].The expression of SOCS3 mRNA and OB-Rb mRNA in newborns from the study group was(1.44±0.29)and(1.33±0.39),respectively,which was significantly greater than that in the control group[(0.33±0.19),(0.50±0.21),t=9.987,P<0.001;t=11.037,P<0.001].Fasting blood glucose and fasting insulin levels as well as insulin resistance index in the study group were(22.06±3.94)mmol/L,(20.02±4.61)mU/L,(19.79±6.29)respectively,which were significantly higher than those in the control group[(11.73±2.92)mmol/L,(13.31±3.43)mU/L,(6.96±2.52),t=8.133,P=0.001;t=4.498,P=0.027;t=7.352,P=0.002].Insulin sensitivity index in the study group was significantly lower than that in the control group[(-6.07±0.32)vs.(-4.98±0.37),t=8.244,P<0.001].Conclusion Obesity before pregnancy and excessive weight gain during pregnancy will increase the expression of SOCS3 mRNA and further affect the expression of STAT3-SOCS3-leptin/insulin signaling pathway in offspring.