Modulation of miRNA Signature in Human Adipose Tissue After 3 Months of ω-3PUFA Supplementation

Obesity is a persistent public health issue, often resulting in metabolic complications such as insulin resistance (IR). The secretion of pro-inflammatory cytokines from adipose tissue (AT) is increased during obesity, contributing to the impairment of systemic insulin sensitivity. While interventions in animal models have shown that reducing inflammation restores insulin sensitivity, human studies reducing systemic inflammation have produced inconsistent results. We recently demonstrated that three months of high-dose (4 g/daily) ω-3PUFA (fish oil, FO) supplementation improved insulin sensitivity, and decreased systemic and AT inflammation in individuals with obesity (BMI  ≥  30 kg/m²). Given recent studies highlighting the involvement of microRNA (miRNA) in inflammatory cytokine production, we investigated the effect of ω-3PUFA supplementation on AT miRNA expression in this cohort. AT biopsies were collected before and after ω-3PUFA supplementation. miRNA was processed on the Affymetrix miRNA 4.0 GeneChip and analyzed using existing inflammatory gene sets sourced from MSigDB. Unbiased, differentially expressed miRNA analysis identified miR-4498 and miR-5689 as significantly increased after three months of ω-3PUFA supplementation. Real-time PCR confirmed bioinformatic analysis findings. Our study reports the modulation of miRNA in AT, reductions in systemic and AT markers of inflammation, and the improvement of IR post ω-3PUFA supplementation. Further research is needed to elucidate the link between miR-4498, miR-5689, and whole-body insulin sensitivity.