Abstract：
Aging affects lipid metabolism and can cause obesity as it is closely related to the disorder of many lipogenic regulatory factors. LncRNAs have been recognized as pivotal regulators across diverse biological processes, but their effects on lipogenesis in aging remain to be further studied. In this work, using RNA sequencing (RNA-Seq), we found that the expression of lncRNA AI504432 was significantly upregulated in the eWAT (epididymal white adipose tissue) of aging mice, and the knockdown of AI504432 notably reduced the expression of several adipogenic genes (e.g., Cebp/α, Srebp-1c, Fasn, Acaca, and Scd1) in senescent adipocytes. The bioinformatics investigation revealed that AI504432 possessed a binding site for miR-1a-3p, and the discovery was verified by the luciferase reporter assay. The expression of Fasn was increased upon the inhibition of miR-1a-3p but restored upon the simultaneous silencing of AI504432. Taken together, our results suggested that AI504432 controlled lipogenesis through the miR-1a-3p/Fasn signaling pathway. The findings may inspire new therapeutic approaches to target imbalanced lipid homeostasis due to aging.
摘要：
衰老影响脂质代谢，并可导致肥胖，因为它与许多脂肪生成调节因子的紊乱密切相关。LncRNAs已被认为是跨不同生物过程的关键调节因子，但是它们对衰老过程中脂肪生成的影响还有待进一步研究。在这项工作中,使用RNA测序（RNA-Seq），我们发现，lncRNAAI504432的表达在衰老小鼠的eWAT（附睾白色脂肪组织）中显著上调，AI504432的敲低显著降低了几种成脂基因的表达(例如，Cebp/α,Srepp-1c,Fasn,Acaca,和Scd1）在衰老的脂肪细胞中。生物信息学研究表明，AI504432具有miR-1a-3p的结合位点，并通过荧光素酶报告基因测定证实了这一发现。Fasn的表达在抑制miR-1a-3p时增加,但在同时沉默AI504432时恢复。一起来看,我们的结果表明,AI504432通过miR-1a-3p/Fasn信号通路控制脂肪生成.这些发现可能会激发新的治疗方法，以针对衰老引起的脂质稳态失衡。
