母鼠营养不良导致子代在生命早期出现糖脂代谢紊乱及其机制探讨

doi:10.16288/j.yczz.2015.01.010

遗传 ›› 2015, Vol. 37 ›› Issue (1): 70-76.doi: 10.16288/j.yczz.2015.01.010

母鼠营养不良导致子代在生命早期出现糖脂代谢紊乱及其机制探讨

郑佳, 肖新华, 张茜, 于淼, 许建萍, 王志新, 刘一静, 李明敏

中国医学科学院,北京协和医学院,北京协和医院内分泌科,卫生部内分泌重点实验室,北京 100730

收稿日期:2014-05-10 修回日期:2014-08-07 出版日期:2015-01-20 发布日期:2015-01-20
通讯作者: 肖新华,教授,博士生导师,研究方向：糖尿病发病机制。E-mail: xiaoxinhua@medmail.com.cn E-mail:xiaoxinhua@medmail.com.cn
作者简介:郑佳,在读博士研究生,研究方向：糖尿病发病机制的表观遗传学研究。E-mail: zhengjiapumc@163.com
基金资助:
国家自然科学基金项目(编号：81170736)资助

PPARγ links maternal malnutrition and abnormal glucose and lipid metabolism in the offspring of mice

Jia Zheng, Xinhua Xiao, Qian Zhang, Miao Yu, Jianping Xu, Zhixin Wang, Yijing Liu, Mingmin Li

Key Laboratory of Endocrinology of Ministry of Health; Department of Endocrinology, Peking Union Medical College Hospital; Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Received:2014-05-10 Revised:2014-08-07 Online:2015-01-20 Published:2015-01-20

摘要/Abstract

摘要： 为了探讨母鼠孕期和哺乳期营养不良对子代生命早期糖脂代谢的影响及其机制,文章对孕期和哺乳期母鼠分别喂养高脂饮食、低蛋白饮食和正常饮食,观察其子鼠断乳时(3周龄)糖脂代谢指标,并采用荧光定量PCR方法检测子鼠肝组织氧化物酶增殖物激活受体γ(PPARγ)基因的表达情况。结果表明：子鼠在3周龄时,与正常饮食组相比,低蛋白饮食组子鼠出生体重(7.36±0.91 vs 8.94±1.39,P<0.0001)较低,体长较短(12.27±0.53 vs 13.44±0.36,P<0.0001);高脂饮食组子鼠体重(9.53±0.68 vs 7.36±0.91,P<0.0001)和体长(13.22±0.35 vs 12.27±0.53,P<0.0001)均高于低蛋白饮食组;另外,高脂饮食组子鼠腹腔糖耐量实验30 min和60 min血糖明显高于正常饮食组(P<0.001),且高脂饮食组30 min血糖水平也明显高于低蛋白饮食组(P<0.001),高脂饮食组子鼠糖耐量曲线下面积明显大于正常饮食组(P<0.001)。另外,与正常饮食组相比,高脂饮食组子鼠空腹胆固醇水平明显升高(1.64±0.21 vs 1.18±0.16,P<0.01),低蛋白饮食组空腹胆固醇水平明显下降(0.96±0.09 vs 1.18±0.16,P<0.05)。荧光定量PCR结果显示,在低蛋白饮食组和高脂饮食组,其子鼠肝组织PPARγ基因表达量均明显高于正常饮食组(P<0.05)。结果显示,母鼠妊娠期和哺乳期高脂饮食与低蛋白饮食均可以诱导子鼠在发育早期出现糖脂代谢紊乱,PPARγ基因可能在其中参与了重要的调控作用。

关键词: 母体营养, 糖脂代谢, 子鼠, PPARγ

Abstract: Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that regulate gene transcription. PPARs play essential roles in modulating cell differentiation, development, and metabolism (carbohydrate, lipid, protein). Here, we investigated whether PPARγ plays a role in linking maternal malnutrition and aberrant metabolism in the offspring of mice. After feeding dams with high fat (HF) and low protein (LP) diet during pregnancy and lactation, we examined the effects on the offspring at weaning (age of 3-week). The results showed that the LP offspring had lower body weight and length than the control. The HF offspring had heavier body weight and longer body length than LP. The blood glucose levels in HF group were significantly higher at 30 min and 60 min after intraperitoneal glucose administration and the area under curve was also significantly larger than the control. The blood glucose levels in HF group were significantly higher at 30 min than LP. HF group had elevated total cholesterol levels and LP group had decreased total cholesterol levels compared with the control. All results were statistically significant as examined by t-test. More importantly, PPARγ expression levels detected by qRT-PCR were significantly increased in HF and LP groups compared with the control. In conclusion, maternal HF and LP diet during pregnancy and lactation can induce impaired glucose and lipid metabolism in the early life of mouse offspring, where PPARγ may play an important role.

Key words: maternal nutrition, glucose and lipid metabolism, mice, PPARγ

郑佳, 肖新华, 张茜, 于淼, 许建萍, 王志新, 刘一静, 李明敏. 母鼠营养不良导致子代在生命早期出现糖脂代谢紊乱及其机制探讨[J]. 遗传, 2015, 37(1): 70-76.

Jia Zheng, Xinhua Xiao, Qian Zhang, Miao Yu, Jianping Xu, Zhixin Wang, Yijing Liu, Mingmin Li. PPARγ links maternal malnutrition and abnormal glucose and lipid metabolism in the offspring of mice[J]. HEREDITAS(Beijing), 2015, 37(1): 70-76.

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母鼠营养不良导致子代在生命早期出现糖脂代谢紊乱及其机制探讨

PPARγ links maternal malnutrition and abnormal glucose and lipid metabolism in the offspring of mice

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