1. Long noncoding RNA AI504432 upregulates FASN expression by sponging miR-1a-3p to promote lipogenesis in senescent adipocytes.
- Author
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Wang, Shuwen, Wang, Rui, Hu, Yaqi, Zhang, Yifan, Yuan, Qi, Luo, Yiyang, and Yuan, Chengfu
- Subjects
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GENE expression , *LINCRNA , *LIPID synthesis , *WHITE adipose tissue , *ADIPOSE tissues , *FATTY acid synthases , *HOMEOSTASIS , *FAT cells - 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. [Display omitted] • Lipogenesis is significantly increased in aging mice and senescent adipocytes. • LncRNA AI504432 promotes lipid synthesis both in vivo and in vitro. • miR-1a-3p is a downstream target of lncRNA AI504432. • LncRNA AI504432 mediates Lipogenesis via the miR-1a-3p/FASN pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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