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<p>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.</p> Graphic Abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2026年4月8日

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  • Driele N. Garcia,
  • Bianka M. Zanini,
  • Sarah A. Ashiqueali,
  • Miguel Brieño-Enriquez,
  • Jeffrey B. Mason,
  • Augusto Schneider,
  • Michal M. Masternak

摘要

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.

Graphic Abstract