An Integrated Analysis of mRNA and lncRNA Expression Profiles Indicates Their Potential Contribution to Brown Fat Dysfunction With Aging
An Integrated Analysis of mRNA and lncRNA Expression Profiles Indicates Their Potential Contribution to Brown Fat Dysfunction With Aging
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mRNA 和 lncRNA 表达谱的综合分析表明它们对衰老引起的棕色脂肪功能障碍的潜在贡献
DOI：
10.3389/fendo.2020.00046
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发表时间：
2020-02-17
影响因子：
5.2
通讯作者：
Cui, Xianwei
中科院分区：
文献类型：
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作者：
Feng, Jie;Xu, Haoqin;Cui, Xianwei
棕色脂肪组织（BAT）可以将脂肪酸和葡萄糖转化为热量，具有对抗肥胖和糖尿病的潜力。 BAT 的质量和活性随着年龄的增长而逐渐减少。作为新发现的基因表达调节因子，长链非编码RNA（lncRNA）在生命过程中表现出广泛的功能。然而，长链非编码RNA（lncRNA）是否与衰老过程中的BAT功能障碍有关尚不清楚。在这里，我们使用 RNA 测序技术，鉴定出 3237 个信使 RNA (mRNA) 和 1312 个 lncRNA 在 10 个月大的小鼠的 BAT 中与 6 至 8 周大的小鼠相比存在差异表达。蛋白质-蛋白质相互作用网络和k-score分析表明，核心mRNA与两个重要的衰老相关通路相关，包括细胞周期和p53信号通路。基因集富集分析表明这些 mRNA 可能参与脂质代谢和棕色脂肪功能障碍。功能富集分析表明，失调的 lncRNA 与线粒体、细胞衰老调节、细胞周期、代谢和 p53 信号通路相关。此外，我们发现两种lncRNA（NONMMUT024512和n281160）可能参与其邻近基因过氧化物酶体增殖物激活受体α（Pparα）（一种生热调节剂）的调节。总的来说，这些结果为lncRNA在年龄相关生热降解中的作用的广泛研究奠定了基础。
Brown adipose tissue (BAT) can convert fatty acids and glucose into heat, exhibiting the potential to combat obesity and diabetes. The mass and activity of BAT gradually diminishes with aging. As a newly found regulator of gene expression, long non-coding RNAs (lncRNAs) exhibit a wide range of functions in life processes. However, whether long non-coding RNA (lncRNA) involves in BAT dysfunction with aging is still unclear. Here, using RNA-sequencing technology, we identified 3237 messenger RNAs (mRNAs) and 1312 lncRNAs as differentially expressed in BAT of 10-months-old mice compared with 6- to 8-week-old. The protein-protein interaction network and k-score analysis revealed that the core mRNAs were associated with two important aging-related pathways, including cell cycle and p53 signaling pathway. Gene set enrichment analysis indicated that these mRNAs might participate in lipid metabolism and brown fat dysfunction. Functional enrichment analyses demonstrated that dysregulated lncRNAs were associated with mitochondria, regulation of cellular senescence, cell cycle, metabolic and p53 signaling pathways. Moreover, we revealed that two lncRNAs (NONMMUT024512 and n281160) may involve in the regulation of their adjacent gene peroxisome proliferator-activated receptor alpha (Pparα), a thermogenesis regulator. Collectively, these results lay a foundation for extensive studies on the role of lncRNAs in age-related thermogenic degradation.