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Background: MicroRNA-33 may control a wide range of different metabolic functions., Methods: This study aims to assess the miR-33a circulating profile in normal-weight (N = 20) and obese (O = 30) adolescents and to correlate its expression levels to their metabolic parameters. In a subset of subjects, we compared circulating miR-33a with exosomal miR-33a., Results: Metabolic parameters were altered in O, with initial hyperinsulinemia. Circulating miR-33a was significantly higher in O than in N ( p = 0.0002). Significant correlations between miR-33a and auxological and metabolic indices (Insulin p = 0.01; Cholesterol p = 0.01; LDL p = 0.01; HbA1c p = 0.01) were found. Splitting our population (O + N) into two groups, according to the median value of mRNA expression miR-33a levels (0.701), irrespective of the presence or absence of obesity, we observed that those having a higher expression of miR-33a were more frequently obese (87.5% vs. 12.5%; p < 0.0001) and had significantly increased values of auxological and metabolic parameters. Exosomes extracted from plasma of N and O carried miR-33a, and its expression was lower in O ( p = 0.026). No correlations with metabolic parameters were observed., Conclusion: While exosome miR-33a does not provide any advantage, circulating miR-33a can provide important indications in an initial phase of metabolic dysfunction, stratifying obese adolescents at higher cardiometabolic risk.