Mitochondrial dysfunction in COPD patients with low body mass index

Abstract

Patients with chronic obstructive pulmonary disease (COPD) show abnormal adaptations of skeletal muscle redox status after exercise training. Increased skeletal muscle oxidative stress in COPD patients may prompt mitochondrial dysfunction.The present study explores the association between body composition and mitochondrial respiration in seven COPD patients with low body mass index (BMIL), eight COPD patients with normal body mass index (BMIN) and seven healthy controls. All of them underwent a vastus lateralis biopsy in which muscle structure, in vitro mitochondrial respiratory function, uncoupling protein 3 (UCP3) mRNA expression and glutathione levels in both isolated mitochondria and the whole muscle were determined.Mitochondrial respiratory function (assessed by acceptor control ratio (ACR)) was impaired in BMIL (2.2¡0.6) compared with both BMIN (5.3¡1.3) and controls (8.2¡1.3). ACR significantly correlated with arterial oxygen tension and with muscle endurance but it showed a negative association with exercise-induced increase in blood lactate levels. UCP3 mRNA expression was reduced in BMIL patients.In conclusion, chronic obstructive pulmonary disease patients with low body mass index show electron transport chain dysfunction, which may contribute to low muscle endurance in the current subgroup of patients.

Peroxisome proliferator-activated receptors: a therapeutic target in COPD?

“…Data regarding expression of inflammatory genes in relation to NF-kB activation are, however, lacking. Furthermore, some studies reported increased levels of inflammatory markers, including tumour necrosis factor (TNF)-a protein, in skeletal muscle of COPD patients [36,37], while others did not [38]. This discrepancy may be related to differences in COPD phenotypes and muscles studied.…”

Mitochondrial dysfunction in COPD patients with low body mass index

“…Accordingly, we read with great interest the article by RABINOVICH et al [2], which was recently published in the European Respiratory Journal. RABINOVICH et al [2] showed that chronic obstructive pulmonary disease (COPD) patients with a low body mass index (BMI; 19.2¡0.6 kg?m -2 ) have a dysfunctional mitochondrial electron transport chain in comparison with COPD patients with a ''normal'' BMI (29.0¡1.7 kg?m -2 ) and healthy controls (27.9¡1.9 kg?m -2 ). The function of the mitochondrial electron transport chain was assessed as acceptor control ratio (i.e.…”

“…In the study performed by RABINOVICH et al [2], the prevalence of current and past smoking was not reported. As a consequence, the potential influence of smoking on the outcome of the study was neither analysed nor discussed.…”

“…As a consequence, the potential influence of smoking on the outcome of the study was neither analysed nor discussed. Due to our recent observations, and reports from other groups about the induction of mitochondrial dysfunction by cigarette smoke even in circulating cells that do not reside in pulmonary tissues [4], we thought it would be very interesting to know how the results of the clinical study performed by RABINOVICH et al [2] would appear if current (and past) smoking were taken into account. Furthermore, it would be interesting to know how the significantly lower acceptor control ratio results reported in their study affect the principal function of mitochondria: adenosine triphosphate production.…”

Age-graded reductions in quadriceps muscle strength and peak aerobic capacity in COPD

“…Patients with COPD have a significantly lower mitochondrial density 33 and activity 34 , as well as a lower oxidative enzyme activity 35 and a lower mechanical efficiency 36 . There are also fewer capillaries per muscle fiber in patients with COPD.…”