Structured exercise programs are of great benefit in order to obtain a proper glycemic control in subjects with type diabetes (T2D). However, whether the metabolic effects of aerobic (AER) and resistance (RES) exercise exert specific changes in the expression profile of circulating miRNAs (c-miRNAs) is still largely unknown. We studied 24 individuals with T2D from the RAED2 Trial (NCT01182948), randomly assigned to AER or RES training protocols (NAER=12; NRES=12). Firstly, the baseline and post-training levels of 179 c-miRNAs were measured by RT-PCR in 6 individuals (NAER=3; NRES=3). Nineteen c-miRNAs exhibited at least 20% fold-change variation from baseline and were thereafter measured in the whole group. Compared to baseline, the expression levels of miR-423-3p, miR-451a and miR-766-3p resulted significantly upregulated after exercise, irrespective of exercise type (type I error rate threshold: 0.0026; 0.05/19 miRNAs). Bioinformatic analysis by miRSystem and Diana Tools revealed that these c-miRNAs targeted genes involved in pathways relevant to fatty acids biosynthesis and metabolic regulation, including LKB1, PI3K, mTOR and IRS signaling pathways. Interestingly, miR-451a and miR-423-3p changes were positively correlated with fat loss after training (rho=0.45 and 0.43, respectively; p<0.05). Both miRNAs, alone or in combination, resulted as independent predictors of fat loss, when entered in generalized linear models including exercise type as covariate. However, only miR-451a eventually survived as predictor of fat loss after further correction for age, sex, BMI and hemoglobin A1c.

In conclusion, physical exercise in individuals with T2D is associated with specific changes of c-miRNAs profile, predominantly clustered along pathways with regulatory significance for fatty acid metabolism. Further investigations are warranted to confirm our findings and to unravel their mechanistic significance.


D. Olioso: None. M. Dauriz: None. E. Bacchi: None. C. Negri: None. E. Bonora: None. P. Moghetti: None.

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