Circulating miR-122 and miR-139-3p: Association with Lipid, Inflammatory, and Glycemic Profile in Adolescents with Insulin-Resistant and Overweight

Background/Objectives: Insulin resistance (IR) in adolescents contributes to the development of metabolic and immunological alterations. These alterations can lead to chronic, systemic, low-grade inflammation in adulthood. Evidence suggests that alterations in miRNA expression play a significant role in the onset of IR by influencing insulin signaling pathways. Therefore, identifying specific miRNAs may aid in the early diagnosis of cardiometabolic risk, particularly during the transition from adolescence to adulthood. Methods: This population-based study aimed to analyze the expression of 21 miRNAs in the plasma of adolescents. We considered IR status, overweight, sex, and age for the analyses. The study measured miRNA expression in plasma samples from 187 adolescents aged 12 to 19 years from the cross-sectional study of the 2015 São Paulo Health Survey (ISA-Nutrition). MiRNA expression was assessed using Exiqon® assays on Fluidigm® technology (Les Ulis, France). Statistical analyses were performed to identify differences in miRNA expression and correlations between variables, using a complex research design to ensure representativeness at the population level. Results: The incidence of IR and overweight was high in adolescents (44% and 33%, respectively). High-sensitivity C-reactive protein (hs-CRP) concentration was higher in overweight adolescents. IR was correlated with higher plasma expression of miR-122 and miR-139-3p. Furthermore, miR-486, miR-363, miR-30d, miR-28, miR-223, miR-21, miR-146, miR-130b, miR-126, miR-122, and miR-139-3p showed specific correlations with individual risk for IR, sex, and adolescent stage. Conclusions: The miRNAs showed differential expression according to sex and adolescent stage, and were correlated with cardiometabolic risk factors, suggesting their potential utility for early screening in adolescents. The study highlights age- and sex-related differences in miRNA levels between adolescents with IR and overweight. The cross-sectional design is a limitation of this study, as we cannot infer causality for the associations observed here.