Impact of miR-181a-5p and miR-1249-3p treatment on the visceral adipose tissue transcriptome of female mice.

MicroRNAs (miRNAs) regulate gene expression and can influence processes such as inflammation, metabolism, and aging. This study assessed the effects of miR-181a-5p and miR-1249-3p mimics on the transcriptome of visceral adipose tissue in middle-aged females mice. Mice received intraperitoneal injections of either miR-181a-5p, miR-1249-3p, or vehicle control, followed by transcriptomic and metabolic analyses. Both treatments significantly reduced fasting blood glucose levels and promoted overexpression of the respective miRNAs in adipose tissue. RNA-Seq analysis revealed that both miRNAs modulated genes involved in immune regulation, energy metabolism, and insulin signaling. miR-181a-5p predominantly upregulated immune and inflammatory pathways such as Jak-STAT and Toll-like receptor signaling, whereas miR-1249-3p downregulated metabolic pathways related to lipid oxidation and oxidative phosphorylation. Despite opposing effects, both miRNAs induced gene-expression profiles resembling those observed in long-lived, growth hormone-deficient mice, suggesting a shared role in promoting insulin sensitivity and metabolic resilience. These findings highlight miR-181a-5p and miR-1249-3p as potential therapeutic targets for improving metabolic health and delaying age-related dysfunctions in adipose tissue.