A 12-week program of moderate intensity exercise reduces plasma myostatin in HIV-infected subjects

Introduction. We have previously observed that brisk walking, as moderate intensity physical activity, improves bone density in HIV-infected patients treated with cART, as assessed by Dual X-Ray Absorptiometry (DEXA). Aim of this study was to investigate the possible mechanisms underlying this observation and in particular whether muscle stimulation by exercise is associated with a reduced production of myostatin (growth/differentiation factor 8, GDF-8), a negative regulator of muscle growth and osteogenesis. Methods. We analyzed data from 25 subjects, representing a subset of a larger group of HIV-infected, cART-treated, sedentary subjects who were enrolled in a 12-week exercise program. This consisted of 3 outdoor sessions/week of 60 min walking at 65-75% of HR (Heart Rate) max with ("walk/strength" group) or without ("walk" group) 30 min circuit training at 65% of 1-RM (Repetition Maximum). Subjects were examined at baseline (BL) and 12 weeks (W12) by 6-minute walking test (6MWT) and 1-RM test. Myostatin level in plasma was determined by ELISA. Differences between BL and W12 were tested by Wilcoxon-signed paired rank test. Spearman test was used to assess correlations between variables. Results. All participants completed the 12-week program with a median adherence of 64% (IQR 59-75). They were 20M, 5F; median 51 y-o, IQR 47-55. Fifteen subjects were enrolled in the "walk” group and 10 in the "walk/strength" group. At W12, there was a significant improvement of distance by 6MWT (p<0.0001), and of performance in all strength exercises (crunch p= 0.004, lat machine p= 0.002, chest press p= 0.002, leg extension p= 0.004, sitting calf p= 0.006, leg press p= 0.004). Plasma myostatin levels decreased significantly from a BL median value of 20.9 ng/mL (IQR 10.5-27.3) to 13.5 ng/mL (5.1-24.4) at W12 (p=0.006). A larger reduction of myostatin correlated with higher total distance walked during the 12 weeks of the training period (p=0.023) and the distance walked at W12 6MWT (p=0.008). Conclusions. A 12-week program of moderate intensity physical exercise was associated with a reduction of plasma myostatin level. We propose a model by which exercise may induce attenuation of myostatin expression from skeletal muscle and, possibly, lead to increased bone density through reduction of its anti-osteogenic potential.