Long non-coding RNAs could act as vectors for paternal heredity of high fat diet-induced obesity.

Long non-coding RNAs could act as vectors for paternal heredity of high fat diet-induced obesity.
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长期的非编码RNA可以充当高脂饮食诱发的肥胖症的父亲遗传的媒介。

DOI:
10.18632/oncotarget.18138
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发表时间:
2017-07-18
期刊:
影响因子:
--
通讯作者:
Jiang G
Jiang G
中科院分区:
其他
文献类型:
--
作者:
An T;Zhang T;Teng F;Zuo JC;Pan YY;Liu YF;Miao JN;Gu YJ;Yu N;Zhao DD;Mo FF;Gao SH;Jiang G

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长链非编码RNA(lncRNA)在表观遗传调控中起重要作用,其异常可能导致男性不育。为了研究lncRNA是否参与肥胖和肥胖诱导的生育力下降的代际遗传,我们将小鼠分为肥胖(喂食高脂饮食的F0小鼠,F0-HFD)和非肥胖(喂食正常食物的F0小鼠,F0-NC)模型组及其雄性后代(分别为F1-HFD和F1-NC)。我们检查了F0-HFD/F0-NC和F1-HFD/F1-NC组中lncRNA和mRNA表达水平的差异。结果显示,在lncRNA和mRNA水平上,F1-HFD/F0-HFD组中的表达模式相似。在F0-HFD和F0-NC组之间观察到lncRNA表达的最大差异。本研究中发现的差异表达的lncRNA靶点和mRNA主要涉及GnRH信号通路、代谢过程和Hippo信号通路; F1-HFD/F0-HFD中类似表达的lncRNA和mRNA与G蛋白偶联受体信号传导途径、胰多肽受体活性和赖氨酸生物合成密切相关,可能在肥胖代际遗传的分子机制中起重要作用。此外,潜在的基因,可能在肥胖相关的低生育力的发病机制中发挥重要作用,揭示了基于微阵列表达谱的lncRNA和mRNA的相互作用的研究。总之,我们发现lncRNA可能通过表达异常参与肥胖导致的不育,这可能是肥胖父系遗传的遗传载体。
Long non-coding RNAs (lncRNAs) play an important role in epigenetic regulation, and abnormalities may lead to male infertility. To investigate whether lncRNAs are involved in intergenerational inheritance of obesity and obesity-induced decline in fertility, we divided mice into obesity (F0 mice fed a high-fat diet, F0-HFD) and non-obese (F0 mice fed normal chow, F0-NC) model groups and their male offspring (F1-HFD and F1-NC, respectively). We examined the differences in the expression levels of lncRNAs and mRNAs in the F0-HFD/F0-NC and F1-HFD/F1-NC groups. The results revealed similar expression patterns in the F1-HFD/F0-HFD groups at both the lncRNA and mRNA levels. The maximum difference in the lncRNA expression was observed between the F0-HFD and F0-NC groups. The differentially expressed lncRNA targets and mRNAs identified in our study are mainly involved in GnRH signalling pathway, metabolic process, and Hippo signalling pathway; similarly expressed lncRNAs and mRNAs in F1-HFD/F0-HFD are closely linked with G-protein coupled receptor signalling pathway, pancreatic polypeptide receptor activity, and lysine biosynthesis, which may play an important role in the molecular mechanism of intergenerational inheritance of obesity. Furthermore, potential genes that might play important roles in the pathogenesis of obesity-related low fertility were revealed by lncRNA-and mRNA-interaction studies based on the microarray expression profiles. In conclusion, we found that lncRNA could be involved in obesity-induced infertility by expressing abnormalities, which could act as genetic vectors of paternal inheritance of obesity.
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