Zinc and circulating microRNAs in women with insulin resistance

Insulin resistance (IR) is a key factor in the development of type 2 diabetes and is potentially associated with zinc deficiency due to the role of this mineral in the metabolism of this hormone. MicroRNAs (miRs) can regulate insulin signaling pathway, glucose metabolism, and inflammation, and their expression can be modulated by different nutrients and bioactive compounds. Nutrimiromics investigates how nutrients modulate gene expression through miRs. However, the associations between miRNAs related to IR mechanisms and zinc status in the body remains unclear. Therefore, this study aimed to evaluate the associations of plasma zinc concentration with the expression of miR-191-5p, miR-188-5p, miR-145-5p, and miR-143-3p in overweight and IR women.

This comparative cross-sectional study included 50 overweight or obese women, aged between 18 and 60 years. IR classification followed Stern's criteria. Circulating miR expression, plasma zinc concentration, biochemical profile, inflammatory biomarkers, and anthropometric parameters were evaluated.

Six percent of the participants had plasma zinc concentrations below the reference value (<70 µg/dL). When categorizing plasma zinc values by their median concentration (≤90 µg/dL and >90 µg/dL), a significant difference was observed in the fibrinogen concentration (p = 0.016) and the expression of three miR evaluated (miR-191-5p, miR-145-5p, and miR-143-3p). A significant inverse correlation was found between plasma zinc concentration and miR-145-5p (p = 0.006), miR-143-3p (p = 0.011), miR-191-5p (p = 0.002), and the serum fibrinogen concentration (p = 0.038). Significant inverse correlations were observed between insulin and miR-191-5p (p = 0.007), miR-188-5p (p = 0.029), miR-145-5p (p = 0.015), and miR-143-3p (p = 0.001). miR-191-5p (p = 0.037) and miR-143-3p (p = 0.021) were inversely correlated with HOMA-IR. The miR-145-5p was negatively correlated with IL-1β (p = 0.006), IL-6 (p = 0.004), and IFN-γ (p = 0.020), and miR-143-3p was negatively correlated with IL-6 (p = 0.018). According to the adjusted logistic regression model, high expression of miR-191-5p (OR=0.06; p = 0.012) was inversely associated with the plasma zinc concentration. In the functional enrichment analysis conducted with the list of target genes, six Gene Ontology (GO) terms were significantly enriched.

All four miRs showed an inverse correlation with insulin, indicating that zinc status may influence miR expression, potentially affecting biological processes involved in IR. This study identified significant expression of miR-143-3p, miR-145-5p, and miR-191-5p at plasma zinc concentrations above 90 μg/dL.