n-3脂肪酸对孕期糖尿病母鼠及其子代糖代谢和Insulin/IGF1信号通路的影响及机理研究

我国2型糖尿病和妊娠期糖尿病的发病率均呈逐年上升趋势。长链n-3多不饱和脂肪酸（n-3 PUFA）C20:5n-3和C22:6n-3的摄入能显著降低亚洲人群胰岛素抵抗和2型糖尿病发病风险。然而，n-3 PUFA对妊娠期糖尿病及其子代的影响仍不清楚。本项目旨在通过对糖尿病Wistar母鼠孕期及哺乳期进行n-3 PUFA干预，研究其对母鼠及子代糖代谢的调节作用及机理。将糖尿病和妊娠期糖尿病母鼠分为糖尿病组、n-3 PUFA干预组及n-3 PUFA缺乏组，探索糖尿病母鼠孕期及哺乳期摄入n-3 PUFA对母鼠及子代糖代谢和胰岛素敏感性的调节作用；对Insulin/IGF1信号通路关键酶活性、关键基因mRNA表达和蛋白表达的影响；对该通路中相关基因甲基化的影响；对子代成长过程中端粒缩短的改善作用以及n-3 PUFA在体内的代谢产物与相关参数的关系来探明n-3 PUFA对糖尿病母鼠及子代的影响及机理。

Prevalence of type 2 diabetes and gestational diabetes mellitus (GDM) increases rapidly in China during the last few years. Higher intake of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) C20:5n-3 and C22:6n-3 is associated with lower risk of insulin resistance and type 2 diabetes in Asian populations. However, the effects of LC n-3 PUFA on diabetic patients and their offspring are still unclear. The aim of the present project is to examine the effects of LC n-3 PUFA supplementation during pregnancy and lactation on the glucose metabolism for the diabetic rats and their offspring and related mechanisms. The present project will establish two diabetic rat models: type 2 diabetes and GDM. In each model, diabetic rats will be divided into three groups: controlled diabetic rats, diabetic rats supplemented with LC n-3 PUFA, and diabetic rats with LC n-3 PUFA deficiency. This project will explore the effects of LC n-3 PUFA on glucose metabolism and insulin sensitivity in diabetic rats and their offspring, and examine the influence of LC n-3 PUFA on enzyme activity, mRNA and protein expression of key genes in the Insulin/IGF1 signaling pathway. In addition, the effects of LC n-3 PUFA supplementation on the methylation of key genes in the Insulin/IGF1 signaling pathway will be explored. Influences of LC n-3 PUFA on the telomere length on different ages of the offspring will be examined. Furthermore, metabonomics technique will be used to determine the in vivo metabolites of LC n-3 PUFA in type 2 diabetes and GDM rats and their offsprings to explore the relationship between the metabolites of LC n-3 PUFA and relevant parameters. Based on the above results to ascertain the effect of LC n-3 PUFA on diabetic pregnant rats and their offspring and its mechanism. The present project will facilitate a better nutritional treatment for the pregnant women with type 2 diabetes or GDM in China.