Aerobic exercise + weight loss decreases skeletal muscle myostatin expression and improves insulin sensitivity in older adults

A S Ryan, G Li, J B Blumenthal, H K Ortmeyer, A S Ryan, G Li, J B Blumenthal, H K Ortmeyer

Abstract

Objective: 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 years, body mass index: 31 ± 1 kg/m(2) , VO2 max: 21.9 ± 1.0 mL/kg/min, X ± Standard error of the mean (SEM)) completed 6 months of 3 days/week 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 h.

Results: Body weight (-8%) and fat mass (-17%) decreased after AEX + WL (P < 0.001). Fat-free mass (FFM) and mid-thigh muscle area by computed tomography did not change but muscle attenuation increased (P < 0.05). VO2 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 before 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 downregulation of myostatin mRNA and an improvement in insulin sensitivity in obese older men and women.

Trial registration: ClinicalTrials.gov NCT00882141.

Conflict of interest statement

Competing Interests

The authors have no competing interests.

Copyright © 2012 The Obesity Society.

Figures

Figure 1
Figure 1
Basal myostatin mRNA levels before and after AEX+WL (n=33). *P

Figure 2

Western blot analysis of myostatin…

Figure 2

Western blot analysis of myostatin protein in human skeletal muscle. ( A )…

Figure 2
Western blot analysis of myostatin protein in human skeletal muscle. (A) The 50-kDa precursor form of myostatin and (B) The small amounts of the 26-kDa mature myostatin were examined by western blotting analysis (upper panel) and the obtained results were quantitatively analyzed (lower panel, n=33). GAPDH served as a reference and was used to correct the difference in sample concentration and loadings. The whole normal human skeletal muscle lysate served as a positive control and an external calibrator to counteract variations in western blotting efficiency. MSTN: myostatin.

Figure 3

Relationship between basal myostatin mRNA…

Figure 3

Relationship between basal myostatin mRNA and glucose utilization, M (n=32) (r=−0.43, P

Figure 3
Relationship between basal myostatin mRNA and glucose utilization, M (n=32) (r=−0.43, P
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Figure 2
Figure 2
Western blot analysis of myostatin protein in human skeletal muscle. (A) The 50-kDa precursor form of myostatin and (B) The small amounts of the 26-kDa mature myostatin were examined by western blotting analysis (upper panel) and the obtained results were quantitatively analyzed (lower panel, n=33). GAPDH served as a reference and was used to correct the difference in sample concentration and loadings. The whole normal human skeletal muscle lysate served as a positive control and an external calibrator to counteract variations in western blotting efficiency. MSTN: myostatin.
Figure 3
Figure 3
Relationship between basal myostatin mRNA and glucose utilization, M (n=32) (r=−0.43, P

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