Can muscle protein metabolism be specifically targeted by exercise training in COPD?

Abstract

Patients with stable chronic obstructive pulmonary disease (COPD) frequently exhibit unintentional accentuated peripheral muscle loss and dysfunction. Skeletal muscle mass in these patients is a strong independent predictor of morbidity and mortality. Factors including protein anabolism/catabolism imbalance, hypoxia, physical inactivity, inflammation, and oxidative stress are involved in the initiation and progression of muscle wasting in these patients. Exercise training remains the most powerful intervention for reversing, in part, muscle wasting in COPD. Independently of the status of systemic or local muscle inflammation, rehabilitative exercise training induces up-regulation of key factors governing skeletal muscle hypertrophy and regeneration. However, COPD patients presenting similar degrees of lung dysfunction do not respond alike to a given rehabilitative exercise stimulus. In addition, a proportion of patients experience limited clinical outcomes, even when exercise training has been adequately performed. Consistently, several reports provide evidence that the muscles of COPD patients present training-induced myogenic activity limitation as exercise training induces a limited number of differentially expressed genes, which are mostly associated with protein degradation. This review summarises the nature of muscle adaptations induced by exercise training, promoted both by changes in the expression of contractile proteins and their function typically controlled by intracellular signalling and transcriptional responses. Rehabilitative exercise training in COPD patients stimulates skeletal muscle mechanosensitive signalling pathways for protein accretion and its regulation during muscle contraction. Exercise training also induces synthesis of myogenic proteins by which COPD skeletal muscle promotes hypertrophy leading to fusion of myogenic cells to the myofiber. Understanding of the biological mechanisms that regulate exercise training-induced muscle growth and regeneration is necessary for implementing therapeutic strategies specifically targeting myogenesis and hypertrophy in these patients.

The Effect of Adding Neuromuscular Electrical Stimulation with Endurance and Resistance Training on Exercise Capacity and Balance in Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial

“…Improvement in leg muscle strength in the ET + RT + NMES group could be explained by increasing capillarization and fiber-type plasticity [ 26 ]. Besides, another explanation could be taken into consideration that skeletal muscle hypertrophy is achieved by positive protein balance and fusion of satellite cells to myofibers after exercise training in COPD patients [ 26 ]. Similar to what was found in previous studies, leg muscle strength has improved significantly more in the ET + RT + NMES group than in the ET + RT group [ 21 ].…”

Locomotor Muscles in COPD: The Rationale for Rehabilitative Exercise Training

“…Chronic hypoxemia but also tissue hypoxia have been associated with the extent of systemic inflammation (Takabatake et al, 2000;Pitsiou et al, 2002;Baldi et al, 2008) and may be an important factor contributing to loss of fat-free mass (Turan et al, 2011;Simoes and Vogiatzis, 2018). Chronic hypoxia has been associated with an overexpression of muscular DNA damage responses-1 (REDD1) in COPD (Favier et al, 2010), a negative regulator of mammalian target of rapamycin (mTOR) (Brugarolas et al, 2004).…”

“…Of note, cachectic patients with COPD may be particularly prone to deleterious exercise training-induced oxidative and nitrosative stresses: a reduction in antioxidant capacity (Rabinovich et al, 2006) and an increase in protein nitration (Vogiatzis et al, 2010) have been specifically reported following intervention in this subpopulation. Actually, these adverse processes likely hold a prominent role in skeletal muscle wasting in patients with COPD (Simoes and Vogiatzis, 2018). In a recent randomized controlled trial, antioxidant supplementation provided additional effects to rehabilitative exercise training alone on muscle structure and function (e.g., greater gains in type I muscle fiber proportion, antioxidant deficits and muscle strength) although muscle endurance improved similarly in both groups (Gouzi et al, 2019).…”

“…Exercise training may modify the balance between myogenesis, protein synthesis and protein breakdown in favor of an exerciseinduced anabolism in COPD (Simoes and Vogiatzis, 2018).…”

A relação entre a doença pulmonar obstrutiva crônica e a função muscular esquelética: revisão de literatura

“…Esse deslocamento para fibras glicolíticas está associado ao aumento da mortalidade, sendo que o treinamento físico para pacientes com DPOC pode apenas reverter parcialmente essa mudança de tipo de fibra. Porém, pacientes com frequência aumentada de exacerbações da DPOC diminuem sua tolerância à caminhada, definindo o desuso como outro agravante para as alterações evidentes(GOSKER, 2014, BARREIROS, 2018, SIMOES, 2018, SHARANYA, 2019, OBEREZHETS, MOSTOVOY, DEMCHUCK, 2019.Além disso, cabe destacar que, através de estudos de coorte, SHARANYA, 2019 observou que mulheres com DPOC têm uma maior prevalência de sinais de atrofia das fibras de tipo II e perda de força do quadríceps quando comparadas com homólogos masculinos, acima das diferenças normais entre os sexos na saúde. Consistentemente, as pacientes afetadas do sexo feminino têm um menor pico de carga de trabalho e maiores queixas de desconforto Por outro lado, nota-se um expressivo acúmulo de espécies reativas de oxigênio e nitrogênio (ROS / RNS), já que o tabagismo, a longo prazo, estimula a atividade dos macrófagos alveolares e neutrófilos advindos da circulação, que liberam radicais superóxido e peróxido de hidrogênio.…”