Ma Feifei, Li Wei, Tang Renqiao, Liu Zhuo, Ouyang Shengrong, Cao Dingding, Li Yuanyuan, Wu Jianxin
Department of Biochemistry, Capital Institute of Pediatrics, Beijing, China.
Graduate School, Chinese Academy of Medical Science, Beijing, China.
Cell Physiol Biochem. 2017;42(1):416-426. doi: 10.1159/000477486. Epub 2017 May 25.
BACKGROUND/AIMS: Obesity is a major contributor to the growing prevalence of metabolic and cardiovascular diseases. This study was designed to investigate the effect of folic acid (FA) on obese mice by detecting the genome-wide expression profile of lncRNAs and mRNAs in the heart.
Heart samples were collected from mice fed with standard diet (SD), high-fat diet (HFD) and high-fat diet with FA intake (HFDF). LncRNAs and mRNAs between HFD and HFDF group were analyzed by lncRNA microarray. Nine lncRNAs and mRNAs were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics prediction was used to investigate the potential function of these differentially expressed lncRNAs. Co-expresson analysis was used to determine the transcriptional regulatory relationship of differentially expressed lncRNAs and mRNAs between two groups.
The expression of 58,952 lncRNAs and 20,145 mRNAs in HFD and HFDF groups was profiled by using microarrays. Gene Ontology and pathway analyses indicated that the biological functions of differentially expressed mRNAs were related to inflammation, energy metabolism, and cell differentiation. Co-expression networks composed of lncRNAs and mRNAs were also constructed to investigate the potential regulatory roles of differentially expressed lncRNAs on mRNAs. LncRNAs, namely, NONMMUT033847, NONMMUT070811, and NONMMUT015327, were validated through qRT-PCR, and these lncRNAs may be important factors regulating inflammation, energy metabolism, and cell differentiation. The expression levels of Dnajb1, Egr2, Hba-a1, Il1β, Cxcl2, and Tnfsf9 were significantly different between HFD and HFDF.
Results suggested that FA may improve the cardiovascular function of obesity and contribute to those lncRNAs associated with inflammation and cell differentiation. In a nutshell, the present study identified a panel of lncRNAs and mRNAs that may be potential biomarkers or drug targets relevant to the high-fat diet related obesity.
背景/目的：肥胖是导致代谢性疾病和心血管疾病患病率不断上升的主要因素。本研究旨在通过检测心脏中lncRNA和mRNA的全基因组表达谱，探讨叶酸（FA）对肥胖小鼠的影响。
从小鼠收集心脏样本，这些小鼠分别喂食标准饮食（SD）、高脂饮食（HFD）和摄入叶酸的高脂饮食（HFDF）。通过lncRNA微阵列分析HFD组和HFDF组之间的lncRNA和mRNA。使用定量逆转录聚合酶链反应（qRT-PCR）验证9种lncRNA和mRNA。利用生物信息学预测来研究这些差异表达lncRNA的潜在功能。使用共表达分析来确定两组之间差异表达的lncRNA和mRNA的转录调控关系。
使用微阵列分析了HFD组和HFDF组中58,952种lncRNA和20,145种mRNA的表达情况。基因本体论和通路分析表明，差异表达mRNA的生物学功能与炎症、能量代谢和细胞分化有关。还构建了由lncRNA和mRNA组成的共表达网络，以研究差异表达lncRNA对mRNA的潜在调控作用。通过qRT-PCR验证了lncRNA，即NONMMUT033847、NONMMUT070811和NONMMUT015327，这些lncRNA可能是调节炎症、能量代谢和细胞分化的重要因素。HFD组和HFDF组之间Dnajb1、Egr2、Hba-a1、Il1β、Cxcl2和Tnfsf9的表达水平存在显著差异。
结果表明，FA可能改善肥胖小鼠的心血管功能，并有助于调控与炎症和细胞分化相关的lncRNA。简而言之，本研究鉴定了一组lncRNA和mRNA，它们可能是与高脂饮食相关肥胖相关的潜在生物标志物或药物靶点。
