Growth differentiation factor‐15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo

Abstract

BackgroundLoss of muscle mass is a co‐morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor‐15 (GDF‐15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF‐15 may contribute to muscle wasting in COPD.MethodsWe determined the expression of GDF‐15 in the serum and muscle of patients with COPD and analysed the association of GDF‐15 expression with muscle mass and exercise performance. To determine whether GDF‐15 had a direct effect on muscle, we also determined the effect of increased GDF‐15 expression on the tibialis anterior of mice by electroporation.ResultsGrowth differentiation factor‐15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF‐15 was inversely correlated with rectus femoris cross‐sectional area (P < 0.001) and exercise capacity (P < 0.001) in two separate cohorts of patients but was not associated with body mass index. GDF‐15 levels were associated with 8‐oxo‐dG in the circulation of patients consistent with a role for oxidative stress in the production of this protein. Local over‐expression of GDF‐15 in mice caused wasting of the tibialis anterior muscle that expressed it but not in the contralateral muscle suggesting a direct effect of GDF‐15 on muscle mass (P < 0.001).ConclusionsTogether, the data suggest that GDF‐15 contributes to the loss of muscle mass in COPD.

Contemporary publication patterns in the Journal of Cachexia, Sarcopenia and Muscle by type and sub‐speciality: facts and numbers

“…[57][58][59][60][61][62][63] As befits a series of fields that are relatively new and not the main speciality of many practitioners, there was a large number of informative review articles, 64-71 as well as the emergence of reports on patient groups, commentaries, and political campaigns. [57][58][59][60][61][62][63] As befits a series of fields that are relatively new and not the main speciality of many practitioners, there was a large number of informative review articles, 64-71 as well as the emergence of reports on patient groups, commentaries, and political campaigns.…”

“…We conducted an analysis of the types of publications in the respective medical sub-specialities that this major cachexia focussed journal, JCSM, has published in the last three calendar years and analysed trends within each sub-discipline. [57][58][59][60][61][62][63] As befits a series of fields that are relatively new and not the main speciality of many practitioners, there was a large number of informative review articles, 64-71 as well as the emergence of reports on patient groups, commentaries, and political campaigns. Furthermore, they are classified into the major medical sub-specialities (including ageing) or are considered multidisciplinary if applicable across a range of specialities.…”

Klotho and smoking – An interplay influencing the skeletal muscle function deficits that occur in COPD

“…The methodology for this is described elsewhere and is detailed further in the online supplement (22).…”

Metabolic disorders in heart failure and cancer

“…66,67 Likewise, muscle loss disorders frequently occur in 20% of older CHF patients 68 and 30-70% of metastatic cancer patients. 81 In CHF, recent findings 82 postulate a correlation between adiponectin resistance and skeletal muscle impairments. [70][71][72][73] Fulster et al 74 has shown in data from the SICA-HF trial that 20% of CHF patients are affected by muscle wasting.…”