Associação do zinco no plasma com perfil de microRNA circulantes em mulheres com excesso de peso e resistência à insulina

Abstract

Insulin is a hormone secreted by pancreatic β-cells in response to the availability of glucose and circulating fatty acids in the blood, is crucial for metabolic regulation. Insulin resistance (IR) is considered the primary cause of the development of type 2 diabetes, and alterations in the signaling pathway of this hormone may be associated with zinc deficiency, as this mineral plays an essential role in insulin metabolism. MicroRNAs (miRs) act in the regulation of insulin signaling pathways, glucose metabolism, and inflammatory response. Excess or deficiency of nutrients can modulate miR expression and influence the risk of developing diseases. However, the association of miRs related to IR mechanisms with the body's zinc status is not clear. Thus, the aim of this study was to evaluate the association of plasma zinc with the expression of miR-191- 5p, miR-188-5p, miR-145-5p, and miR-143-3p in overweight and insulin-resistant women. This cross-sectional study was conducted on 50 women aged between 18 and 60 years, with overweight or obesity, treated at the Endocrinology and Metabology Service of the Hospital das Clínicas of the Faculty of Medicine of USP. The classification of IR was performed according to Stern's criteria. Evaluations were conducted on the expression of circulating miRs, plasma zinc concentration, biochemical profile, inflammatory parameters, and anthropometric measures. Of the participants, 6% had plasma zinc concentrations below the reference value (<70 µg/dL). By categorizing plasma zinc values by their median (≤90 µg/dL and >90 µg/dL), a significant difference was observed in fibrinogen concentration (p=0.016). There was a significant inverse correlation between plasma zinc and miR-145-5p (r=-0.384; p=0.006), miR-143-3p (r=-0.357; p=0.011), miR-191-5p (r=-0.428; p=0.002), and serum fibrinogen concentration (r=-0.295; p=0.038). MiR-191-5p (r=-0.374; p=0.007), miR-188-5p (r=-0.326; p=0.029), miR-145-5p (r=-0.342; p=0.015), and miR-143-3p (r=-0.452; p=0.001) were inversely correlated with insulin. MiR-191-5p (r=-0.296; p=0.037) and miR143-3p (r=-0.327; p=0.021) showed a significant inverse correlation with HOMAIR. In inflammatory parameters, miR-145-5p presented a negative correlation with IL-1β (r=-0.380; p=0.006), IL-6 (r=-0.400; p=0.004), and IFN-γ (r=-0.328; p=0.020), and miR-143-3p with IL-6 (rho=-0.334; p=0.018). In the adjusted logistic regression model, high expression of miR-191-5p (OR=0.06; p=0.012) was inversely associated with plasma zinc concentration. In the functional enrichment analysis performed with the list of target genes, six terms of gene ontology were significantly enriched. Therefore, this study identified three miRs significantly expressed at plasma zinc concentrations above 90 µg/dL: miR-143- 3p, miR-145-5p, and miR-191-5p, and all evaluated miRs showed an inverse correlation with insulin. These data suggest that zinc status may influence the expression of these miRs, potentially impacting the biological processes involved in IR.