Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease

Abstract

Background: Growth differentiation factor 11 (GDF11) is reported to possess anti-aging and rejuvenating effects, including muscle regeneration and to be highly expressed in skeletal muscle. Recently, we demonstrated that the levels of plasma GDF11 were decreased in COPD. However, the effect of decreased circulating GDF11 in the pathophysiology of COPD remains unknown. The aim of this study is to investigate the association between the plasma GDF11 levels and various clinical parameters in patients with COPD.

Patients and methods: Eighteen ex-smokers as control subjects and 70 COPD patients participated in the current study. We measured the levels of plasma GDF11 using immunoblotting, lung function, physical activity using a triaxial accelerometer, quadriceps strength, exercise capacity, and systemic inflammatory markers. We investigated the association between the levels of plasma GDF11 and these clinical parameters.

Results: The levels of plasma GDF11 in the COPD patients had significant positive correlations with the data of lung function. Furthermore, the levels of plasma GDF11 were significantly correlated with the physical activity, quadriceps strength, and exercise capacity. Moreover, the levels of plasma GDF11 were significantly correlated with the data of inflammatory markers. Although various factors were related to GDF11, the multiple regression analysis showed that physical activity was significantly associated with the levels of plasma GDF11.

Conclusion: Physical inactivity was significantly related to the decreased GDF11 levels in COPD, which might be useful for understanding the pathogenesis of COPD. Clarifying the relationships between the physical inactivity and GDF11 may reveal a potentially attractive therapeutic approach in COPD via increasing the plasma levels of GDF11.

Keywords: COPD; muscle strength; physical activity; rejuvenating factor.

Figure 1

Correlations between the levels of GDF11 and lung function data. Notes: Correlations between the levels of plasma GDF11 and the values of FEV₁ % predicted (A), FVC % predicted (B), IC (C), and D_Lco’ % predicted (D) were investigated. Data were statistically analyzed by the Spearman’s rank test. Closed circles (gray): GOLD stage I/II; closed circles (black): GOLD stage III/IV. Abbreviations: D_Lco’, diffusing capacity of the lung for carbon monoxide; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GDF11, growth differentiation factor 11; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IC, inspiratory capacity.

Figure 2

Correlations between the levels of GDF11 and physical activity. Notes: Correlations between the levels of plasma GDF11 and parameters of physical activity including the number of steps (A), duration of ≥2.0 METs (B), ≥2.5 METs (C), and ≥3.0 METs (D) were investigated. r is the correlation coefficient. Data were statistically analyzed by the Spearman’s rank test. Closed circles (gray): GOLD stage I/II; closed circles (black): GOLD stage III/IV. Abbreviations: GDF11, growth differentiation factor 11; GOLD, Global Initiative for Chronic Obstructive Lung Disease; METs, metabolic equivalents.

Figure 3

Correlations between the levels of GDF11 and muscle strength and exercise capacity. Notes: Correlations between the levels of plasma GDF11 and the QMVC % predicted (A) and the 6MWD (B) were investigated. r is the correlation coefficient. Data were statistically analyzed by the Spearman’s rank test. Closed circles (gray): GOLD stage I/II; closed circles (black): GOLD stage III/IV. Abbreviations: GDF11, growth differentiation factor 11; GOLD, Global Initiative for Chronic Obstructive Lung Disease; 6MWD, 6-minute walking distance; QMVC, quadriceps maximal voluntary contraction.

Figure 4

Correlations between the levels of GDF11 and systemic inflammatory markers. Notes: Correlations between the levels of plasma GDF11 and the amounts of IL-6 (A), hs-CRP (B), fibrinogen (C), and MDA (D) were investigated. r is the correlation coefficient. Data were analyzed by the Spearman’s rank test. Closed circles (gray): GOLD stage I/II; closed circles (black): GOLD stage III/IV. Abbreviations: GDF11, growth differentiation factor 11; GOLD, Global Initiative for Chronic Obstructive Lung Disease; hs-CRP, high sensitivity C-reactive protein; IL-6, interleukin-6; MDA, malondialdehyde.