Physical Activity Modulates the Overexpression of the Inflammatory miR‐146a‐5p in Obese Patients

Specific microRNAs (miRs), including the “angio‐miR‐126” and the “inflamma‐miR‐146a‐5p,” have been proposed as biomarkers and even therapeutic targets of obesity‐associated metabolic diseases. Physical activity, a key measure of prevention for obesity and its complications, is reported to influence the expression of these miRs. In this study, we investigate whether a physical activity program proven to improve metabolic parameters in obese patients can correct the circulating levels of these miRs. Plasma miR‐126 and miR‐146a‐5p were measured in a cohort of obese patients ( n = 31, 16F + 15M) before and after the 3‐month physical activity program of the CURIAMO trial (registration number for clinical trials: ACTRN12611000255987) and in 37 lean controls (24F + 13M). miR‐146a‐5p, but not miR‐126, was significantly increased in obese patients as compared with lean controls and decreased in approximately two‐thirds of the participants post‐intervention with a response that positively correlated with pre‐intervention levels of this miR. Waist circumference, the inflammatory cytokine IL‐8 and lipid parameters, principally total cholesterol, showed the strongest correlation with both the baseline levels and post‐intervention correction of miR‐146a‐5p. Post‐hoc analysis of experimental data supports the use of miR‐146a‐5p as a biomarker and predictor of the clinical response to physical activity in obese patients. Furthermore, miR‐146a‐5p expression was confirmed to increase together with that of the inflammatory genes TLR4, NF‐κB, IL‐6, and TNF‐α in LPS‐stimulated human mononuclear leukocytes. In conclusion, the inflamma‐miR‐146a‐5p can serve as a personalized predictor of clinical outcome in obese patients entering physical activity weight‐reduction programs. © 2018 IUBMB Life, 70(10):1012–1022, 2018