过氧化物酶体增殖物激活受体γ(PPARγ)在生长追赶致SGA胰岛素抵抗中的作用和分子机制

项目名称： 过氧化物酶体增殖物激活受体γ(PPARγ)在生长追赶致SGA胰岛素抵抗中的作用和分子机制

项目编号： No.81471017

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 邓红珠

作者单位： 中山大学

项目金额： 70万元

中文摘要： 小于胎龄儿（SGA）与成年期代谢综合征、胰岛素抵抗有关，但具体机制尚不清楚。生长追赶是SGA儿童生后早期的普遍事件，我们前期研究证实SGA胰岛素水平与生长追赶正相关，并首次发现生长追赶SGA大鼠脂肪组织发育异常伴随出生后内脏脂肪过量贮存。有研究显示PPARγ在脂肪细胞分化和脂代谢中起重要作用，故我们推测生长追赶SGA通过PPARγ通路参与体脂追赶和胰岛素抵抗的发生。本项目应用孕鼠饮食限制法制作生长追赶SGA大鼠模型，通过PPARγ激动剂/拮抗剂干预实验，同时应用高蛋白饮食干预获得有线性生长追赶而无体脂追赶SGA大鼠，从组织和分子层面研究内脏脂肪细胞PPARγ表达上调对脂质代谢关键酶、脂肪细胞功能的影响及年龄变化规律，研究PPARγ表达活化在有/无体脂追赶时脂肪和肝脏组织PI3K/Akt信号通路的改变，阐明SGA发生胰岛素抵抗的分子机制及其与体脂追赶的关联性，为寻找新的干预靶点提供科学依据。

中文关键词： 胰岛素抵抗；过氧化物酶体增殖物激活受体γ；生长追赶；小于胎龄儿

英文摘要： Epidemiological studies have demonstrated that the children born small for gestational age (SGA) are at risk of developing metabolic diseases in adulthood. But the biological mechanisms are still largely unknown. Catch-up growth (CUG) is a general event in SGA children in the first several years of life. Our previous study found that the insulin levels were positively related to catch-up growth in SGA individual, accompany with visceral fat catch-up growth. Studies have shown that PPAR gamma plays an important role in the differentiation of fat cells and lipid metabolism. We speculate that PPAR gamma pathway is involved in the occurrence of SGA body fat catch-up and insulin resistance. This project aims to study on the changes of metabolism axis from the organizational level and molecular level, used by SGA rats with catch-up growth. The expression of visceral adipose tissue PPAR gamma, key enzymes involved in lipid metabolism, the function of adipocytes and the PI3K-Akt pathway were investigated through the PPAR gamma agonist / antagonist intervention and high protein diet intervention, to clarify the molecular mechanism of the effects of PPAR gamma pathway in adipose tissue on the promotion of body fat catch-up growth and insulin resistance in SGA individual. It would provide scientific clues for further new target for intervention.

英文关键词： insulin resistance;PPARγ;catch-up growth;SGA