Aerobic Exercise+Weight Loss Decreases Skeletal Muscle Myostatin Expression and Improves Insulin Sensitivity in Older Adults

OBJECTIVE: We sought to determine whether aerobic exercise training+weight loss (AEX+WL) would affect the expression of myostatin and its relationship with insulin sensitivity in a longitudinal, clinical intervention study DESIGN AND METHODS: Thirty-three obese sedentary postmenopausal women and men (n=17 and 16, age:61±1 yrs, BMI:31±1 kg/m(2), VO(2)max:21.9 ± 1.0 ml/kg/min, X ± SEM) completed 6 months of 3d/wk AEX+WL. During an 80 mU·m(−2)·min(−1) hyperinsulinemic-euglycemic clamp, we measured glucose utilization (M), myostatin, myogenin, and MyoD gene expression by real-time RT-PCR in vastus lateralis muscle at baseline and 2 hrs. RESULTS: Body weight (−8%) and fat mass (−17%) decreased after AEX+WL (P<0.001). FFM and mid-thigh muscle area by CT did not change but muscle attenuation increased (P<0.05). VO(2)max increased 14% (P<0.001). AEX+WL increased M by 18% (P<0.01). Myostatin gene expression decreased 19% after AEX+WL (P<0.05). Basal mRNA myostatin levels were negatively associated with M prior to the intervention (r=−0.43, P<0.05). Insulin infusion increased myoD and myogenin expression before and after AEX+WL (both P<0.001) but basal levels did not change. The insulin effect on myostatin expression was associated with the change in M after AEX+WL (r=0.56, P<0.005). CONCLUSIONS: Exercise and weight loss results in a down-regulation of myostatin mRNA and an improvement in insulin sensitivity in obese older men and women.