LncRNA Gm15232通过miR-192-3p/GCR途径促进衰老小鼠的脂肪生成

Yaqi Hu, Yifan Zhang, Shuwen Wang, Rui Wang, Qi Yuan, Wei Wu, Yibei Gui, Jiale Zhao, Xueqing Li, Yumin He, Chengfu Yuan
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摘要

最近的科学研究强调了长链非编码 RNA(lncRNAs)在多种代谢性疾病中的重要性,但 lncRNAs 在与衰老相关的脂质合成异常中的具体功能和机制尚不清楚。在这项工作中,我们研究了lncRNAs对衰老小鼠脂质代谢的影响,因为大量证据表明衰老会扰乱脂质代谢。结果发现,与成年小鼠相比,lncRNA Gm15232在衰老小鼠附睾白色脂肪组织(eWAT)中的表达明显升高。Gm15232的上调通过抑制miR-192-3p的表达发挥了竞争性内源性RNA(ceRNA)的作用,随后miR-192-3p的下调增加了糖皮质激素受体基因(GCR)的表达,最终刺激了脂肪的合成。因此,Gm15232 的上调通过这一机制增加了脂肪生成。这项研究揭示了治疗与年龄有关的脂质代谢异常的潜在靶点。
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LncRNA Gm15232 Promotes Lipogenesis in Aging Mice Through the miR-192-3p/GCR Pathway.

Recent scientific studies have highlighted the importance of long-chain noncoding RNAs (lncRNAs) in a variety of metabolic diseases, but the specific functions and mechanisms of lncRNAs in aberrant lipid synthesis associated with aging are unknown. In this work, we inspected the effects of lncRNAs on the lipid metabolism in aging mice, as substantial evidence suggests that aging disturbs lipid metabolism. The results revealed that the expression of lncRNA Gm15232 was significantly elevated in the epididymal white adipose tissue of aging mice compared to adult mice. This upregulation of Gm15232 functioned as a competitive endogenous RNA by inhibiting the expression of miR-192-3p, and the ensuing downregulation of miR-192-3p increased the expression of the glucocorticoid receptor gene, which ultimately stimulated fat synthesis. The upregulation of Gm15232 thus increased lipogenesis through this mechanism. This study reveals a potential target for the treatment of age-related abnormalities of lipid metabolism.

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