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代谢综合征的发育程序化：利用第二代测序技术分析母胎高果糖摄取对子代大鼠转录组的影响

赵咏梅, 田佑霖, 吕史提, 吴芎历, 李伟嘉, 华瑜

高雄长庚医院生物医学转化研究所；儿童肾脏科；泌尿科，高雄 83301

摘要

临床证据显示高果糖摄取与代谢综合征现象产生有高度相关性，然而关于母体在怀孕与哺乳期高果糖摄取对子代代谢综合征的发育程序化影响的研究却相对缺乏。本研究利用第二代测序(next-generation sequencing)技术分析母鼠高果糖摄取对新生第一天、离乳后一天(出生后三周)、以及成年期(出生后三个月)子代大鼠脑部、心脏、肾脏与膀胱四个器官转录组的影响。结果显示：(1) 母鼠在怀孕与哺乳期高果糖摄取，会程序化胎鼠使其于成年期产生代谢综合征；(2) 同时，在仔鼠脑部、心脏、肾脏与膀胱四个器官引起不同程度的转录组变化；(3) 在新生第一天子代大鼠，有两个基因，分别是Errfi1 与Ctgf，同时在四个器官中表现受到影响，此现象在子代离乳与成年期则消失；(4) 参与果糖代谢、糖酵解及糖异生、脂肪代谢、以及胰岛素信号传导通路的基因转录也受到不同程度影响，此现象在新生第一天尤为显著。该结果提示，可利用第二代测序技术寻找不同年龄层子代器官特异性受母体高果糖摄取影响的基因转录变化，进而研发代谢综合征发育程序化在不同器官引起病变的可能机制与治疗策略。

关键词： 发育程序化; 代谢综合征; 第二代测序; 转录组

分类号：R339.3;R335

Developmental programming of the metabolic syndrome: Next-generation sequencing analysis of transcriptome expression in a rat model of maternal high fructose intake

CHAO Yung-Mei, TAIN You-Lin, LEU Steve, WU Kay L.H., LEE Wei-Chia, CHAN Julie Y.H.

Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital； Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University； Department of Urology, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 83301

Abstract

Excessive fructose intake is related to a high prevalence of metabolic syndrome, while little attention has been paid to the impact of maternal high-fructose (HF) intake on the development of metabolic syndrome and organ-specific transcriptome alterations in the offspring. We utilized RNA next-generation sequencing (NGS) technology to analyze the transcriptome expression in four organs (kidney, brain, heart, and urinary bladder) from 1-day, 3-week, and 3-month-old male offspring exposed to maternal HF diet. Maternal HF induced various phenotypes of metabolic syndrome in adult male offspring. We observed that maternal HF exposure induces long-term alterations of gene expression in the brain, heart, kidney, and urinary bladder in adult offspring. Different organs do not respond similarly to maternal HF intake. We found that changes in expression of Errfi1 and Ctgf were shared by four organs at 1 day of age. Also, a number of genes regulating fructose metabolism, glycolysis/gluconeogenesis, fatty acid metabolism, and insulin signalling appear to be regulated by maternal HF intake in different organs at 1 day of age. Our NGS results are of significance to the development of maternal interventions in the prevention of maternal HF-induced organ-specific programming, in order to reduce the global burden of metabolic syndrome.

Key words: developmental programming; metabolic syndrome; next-generation sequencing; transcriptome

收稿日期：2016-03-16　　录用日期：2016-08-03

通讯作者：华瑜　　E-mail: jchan@cgmh.org.tw

引用本文：

赵咏梅, 田佑霖, 吕史提, 吴芎历, 李伟嘉, 华瑜. 代谢综合征的发育程序化：利用第二代测序技术分析母胎高果糖摄取对子代大鼠转录组的影响[J]. 生理学报 2016; 68 (5): 557-567.

CHAO Yung-Mei, TAIN You-Lin, LEU Steve, WU Kay L.H., LEE Wei-Chia, CHAN Julie Y.H.. Developmental programming of the metabolic syndrome: Next-generation sequencing analysis of transcriptome expression in a rat model of maternal high fructose intake. Acta Physiol Sin 2016; 68 (5): 557-567 (in Chinese with English abstract).